Acta Psychiatr Scand 2009: 119 (Suppl. 439): 8–26 All rights reserved DOI: 10.1111/j.1600-0447.2009.01382.x

 2009 John Wiley & Sons A/S ACTA PSYCHIATRICA SCANDINAVICA

Clinical overview

Clinical practice recommendations for depression Malhi GS, Adams D, Porter R, Wignall A, Lampe L, OÕConnor N, Paton M, Newton LA, Walter G, Taylor A, Berk M, Mulder RT. Clinical practice recommendations for depression. Objective: To provide clinically relevant evidence-based recommendations for the management of depression in adults that are informative, easy to assimilate and facilitate clinical decision making. Method: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. The recommendations then underwent consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. Results: The clinical practice recommendations for depression (Depression CPR) summarize evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. Conclusion: These up-to-date recommendations provide an evidencebased framework that incorporates clinical wisdom and consideration of individual factors in the management of depression. Further, the novel style and practical approach should promote uptake and implementation.

G. S. Malhi1,2,3, D. Adams1,2, R. Porter4, A. Wignall5, L. Lampe1,2,3, N. OÕConnor3,6, M. Paton2, L. A. Newton2, G. Walter3,5, A. Taylor2, M. Berk7,8,9, R. T. Mulder4 1 CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, 2Northern Sydney Central Coast Mental Health Drug and Alcohol, Northern Sydney Central Coast Area Health Service, 3Discipline of Psychological Medicine, University of Sydney, Sydney, NSW, Australia, 4Department of Psychological Medicine, University of Otago, Christchurch, New Zealand, 5Child and Adolescent Mental Health Services, NSCCAHS, 6 Sydney South West Area Health Service, Sydney, NSW, 7Barwon Health and the Geelong Clinic, Melbourne University, 8Orygen Research Centre, Melbourne University and 9Mental Health Research Institute, Melbourne, Vic., Australia

Key words: major depression; treatment recommendations; clinical practice guidelines; evidence-based review Professor Gin S. Malhi, CADE Clinic, Level 5, Building 36, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia. E-mail: [email protected]

Clinical recommendations

• • • •

The management of depression should be based on a combination of data-driven evidence and clinical experience. Management strategies should be tailored to the individual so as to SET A PACE for treatment that matches the phase of illness. Consideration should be given to the clinical context, potential comorbidities and the quantification of symptom severity using rating scales. Psychological strategies should be given greater consideration.

Additional comments

• • •

8

The clinical practice recommendations (CPR) for depression should be used in conjunction with other recognized sources to guide the management of depression. Practice recommendations or treatment guidelines cannot fully capture the myriad of variables unique to each individual and thus need to be used flexibly alongside consideration of the person, their sociocultural context and availability of resources. The Depression CPR focus on the management of depression in adults. Special populations, comorbidities and novel treatments have not been reviewed in detail.

Depression CPR Introduction

Depression is a common illness that usually emerges early in life and affects women more often than men. Recurrent by nature, unipolar depression is associated with considerable morbidity and a significant risk of mortality through suicide (1). Indeed, amongst the causes for numbers of life years lost, because of disability, illness and premature death, unipolar depression ranks high and is predicted to become the second most important contributor to disability by the year 2020 (2). Surprisingly, despite its prevalence and health costs, depression remains under-diagnosed and poorly managed, partly because it lacks definition as a disease, and prevailing treatment is suboptimal. In clinical practice the symptoms of depression usually occur alongside symptoms of anxiety, substance misuse and personality disorders (3). Therefore, ideally, it would be best to develop recommendations that address complex presentations such as coterminous anxiety and depression; however, the evidence for treatments for depression stems largely from studies that examine singular disorders. Facts and figures

The statistics relating to depression vary according to the diagnostic instrument and classification system used to define the illness; however, some useful key facts and figures are summarized in Box 1.

Box 1. Unipolar depression: facts and figures Epidemiological statistics • Depression is 1.5 to three times as common in females as in males (4– 6). • Twelve-month prevalence rate is 5% and lifetime risk is 15% (6, 7). • Lifetime prevalence of suicide is approximately 2% (hospitalized cohorts 10–15%) (8).

Illness characteristics • Mean age of onset is 27 years, but 40% have first episode by the age of 20 years (9). • Average duration of episodes is 3–4 months (7, 9). • Forty per cent experience recurrence within 12 months (10).

Treatment responsiveness • Antidepressant ⁄ psychological interventions are effective in around 50% (11, 12). • Thirty-three per cent respond to placebo (11, 12). • Thirty-three per cent fail to recover (13).

The aetiology of depression is not fully understood but is most probably multifactorial, involving not only psychological and social factors, but also biological determinants. In addition to the longstanding monoamine hypothesis of depression that postulates a lack of synaptic monoamines, theories that implicate neuroendocrine, genetic and neural markers of vulnerability have been posited (14). Studies in these fields of research have attempted to link depression to markers of psychosocial and biological distress and suggest a complex and varied pathophysiology (15). Phases and phenomenology

In the absence of sufficient knowledge as regards the neurobiology of depression, the best system of diagnosis and classification remains uncertain. Researchers and clinicians use both dimensional and categorical approaches in investigational studies and clinical practice. Added to this, a lack of consensus amongst research groups that have used differing criteria to define clinical depression has made meaningful comparison of studies and the interpretation of findings difficult. For instance, the classification of putative depressive ÔsubtypesÕ has occurred on the basis of symptom profile, severity and chronicity of illness, along with treatment responsivity and comorbidity. Diagnostic differentiation has also been sought according to age of onset and presumed aetiology, especially in the context of medical illnesses. However, as yet, no satisfactory or universally accepted taxonomy has emerged. The two classification systems currently most widely used in clinical practice and research are the DSM-IV (16) and ICD-10 (2) and both use similar symptoms to define clinical depression (see Table 1). However, a closer examination of these two systems immediately raises potential difficulties. For instance, in ICD-10 ÔcategoriesÕ of mild, moderate and severe depression that together essentially form a ÔdimensionÕ are determined on the basis of numbers of symptoms. However, in practice the symptoms of clinical depression lack equivalence. Suicidal ideation, for example, is usually a far more critical symptom than most and yet it is counted and weighted as equal to others when defining depression. The descriptors such as mild, moderate or severe have therefore been used sparingly in these recommendations but could not be omitted altogether, as the majority of research in depression has been conducted using either DSM-IV or ICD-10 definitions to categorize clinical populations. Where possible, depression has been defined in these recommendations according to parameters that have treatment implications. For instance, 9

Malhi et al. Table 1. DSM-IV (16) and ICD-10 (2) major depressive disorder diagnostic criteria: symptoms

Phases of Treatment

Acute

Continuation Relapse

on ssi gre rder Pro diso to

Symptoms

Maintenance Recurrence

Relapse

Syndrome Treatment-resistance

Stages of IIIness

Response

Remission

Recovery

Fig. 1. Course of illness in depression [adapted from Ref. (19)]. Stages of illness – Response: significant reduction in clinical signs ⁄ symptoms (often quantified in studies as a 50% decrease in the score of a rating scale such as HAM-D ⁄ MADRS). Remission: state of minimal or no signs ⁄ symptoms but lacking full functional recovery. Recovery: stable state of minimal or no signs ⁄ symptoms with return to premorbid functioning. Relapse: re-emergence ⁄ worsening of signs ⁄ symptoms prior to having achieved recovery. Recurrence: emergence of signs ⁄ symptoms following recovery. Phases of treatment – Acute Phase: initial phase of treatment with active signs and symptoms. Treatment targets response. Continuation: following remission, treatment continues with a focus on achieving functional improvement. Maintenance: treatment continues until signs and symptoms have fully remitted, and functional recovery has been achieved. It is on this basis that continuation treatment prevents relapse and maintenance treatment prevents recurrence. However, in practice depression does not always manifest as discrete episodes and therefore clinically, such a distinction can be difficult. In many contexts, relapse and recurrence are used interchangeably.

depression marked by particular features such as atypical, melancholic or psychotic symptoms has been described separately and where appropriate, severity has been noted, with the accompanying suggestion that further specificity be sought using rating scales. Specifically, a score of 18–24 on the 17-item Hamilton Depression Rating Scale (HAMD) is regarded as moderate depression in adults and a score ‡25 is considered to be severe (17, 18). However, it is important to note that the Depression CPR generally apply to depression that is not 10

marked by melancholic, atypical or psychotic features and that, where there is evidence for severity-related treatment specificity, an attempt has been made to quantify depressive symptomatology using depression rating scale scores. The graph in Fig. 1 shows the development of depression and its progression through successive stages with treatment. The initial acute phase of treatment, during which there is usually a clinical response, culminates with the remission of symptoms (note that remission as defined in clinical trials

Depression CPR as 50% reduction in rating scale score from baseline, does not necessarily equate to clinical remission) and ongoing successful treatment, during the subsequent continuation phase, ideally eventuates in functional recovery. In practice, treatment often continues into the maintenance phase to further diminish the risk of future recurrence. The Depression CPR have been structured according to these phases of treatment. Additional consideration has then been given to dealing with specific subtypes and managing non-response. Aims of the recommendations

The clinical practice recommendations for depression have been developed to provide a meaningful synopsis of the management of clinical depression. The recommendations have attempted to integrate evidence-based findings and clinical wisdom, and they are presented in a manner that is intended to engage and facilitate uptake and implementation. The recommendations have been structured in relation to each phase of depression with consideration given to both individual factors and clinical context. Material and methods

The Depression CPR have been developed by a team of clinicians and researchers that routinely treat depression in a variety of clinical settings [for a detailed description of the methods see Ref. (20)]. The recommendations attempt to provide a practical overview of managing depression in adults, beginning briefly with clinical assessment and diagnosis. The treatment of depression is then discussed in detail with additional consideration of specific subtypes. Subsequent sections deal with maintaining recovery and preventing relapse, and the management of partial or non-response.

SET Safety

A Assesment: - characterise

Education Therapeutic relationship

Table 2. Definition of levels of evidence criteria used in recommendations Level

NHMRC level of evidence (21)

Level I Level II Level III

Systematic review of all relevant randomized controlled trials (RCT) One or more properly designed randomized controlled trial Well-designed prospective trial (non-randomized controlled trial); Comparative studies with concurrent controls and allocation not randomized; case-controlled or interrupted time series with a control group Case series, either post-test or pretest ⁄ post-test Expert opinion

Level IV Level V

NHMRC, National Health and Medical Research Council.

The strength of the evidence within the Depression CPR has been rated according to the National Health and Medical Research Council (NHMRC) Levels of Evidence criteria (21) as listed in Table 2 [see Ref. (20) for further discussion]. Results The management of depression: Set A Pace

The individual management of depression should be evidence based and at the same time carefully tailored to specific needs. The acronym SET A PACE (see Fig. 2) therefore emphasizes the need to consider the unique circumstances of every individual and underscores the variability of clinical depression in terms of its treatment responsivity. ÔSETÕ-ting the foundation

From the outset, it is important to set the foundation for effective treatment by ensuring safety, providing education and facilitating the formation of a therapeutic alliance (see Box 2). These factors are of paramount importance in the management of depression and should be considered throughout all stages of clinical care from assessment through to maintenance treatment.

PACE Psychological therapy (I) Antidepressant treatment (I)

- calibrate - corroborate - consider

Combination (I) ECT (I)

Fig. 2. Schematic overview of the management of depression. See Boxes 2–4 for detailed explanation. ECT, electroconvulsive therapy.

11

Malhi et al.

Box 2. ÔSETÕ: setting the foundation ÔSÕ: Safety is a priority as depression is a significant risk factor for suicide (22). Ensure a comprehensive risk assessment is completed and ongoing, with particular attention to risk of self-harm. Also consider risk of neglect to self or others (such as malnutrition or emotional neglect of children) and, if applicable, document parental responsibilities. In instances where the risk is high and cannot be managed in the community, hospitalization may be necessary. ÔEÕ: Educate the affected individual and, where appropriate, the family ⁄ carer about the illness, treatment options and possible consequences. Psychoeducation and structured problem solving are effective interventions for the treatment of depression in primary care (23–25) and should be routinely provided. Recommend lifestyle changes (sleep hygiene, regular exercise, reduction in alcohol, smoking and illicit drugs and anxiety management) to assist recovery (26–28). ÔTÕ: Therapeutic relationship begins at the time of assessment and remains integral throughout treatment. Irrespective of the therapeutic modality used in the treatment, the relationship between the therapist and patient is an important factor in the process that governs the outcome. Specifically, the quality of the therapeutic relationship, as perceived by the patient, the therapistÕs overall expectation of change and continuity of care have been shown to independently predict treatment outcome (29).

ÔAÕssessment

The factors that govern treatment choice (PACE) and treatment response are determined by a comprehensive ÔAssessmentÕ (see Box 3). Box 3. ÔAÕ: assessment Foresee (4C) treatment outcome It is important at the time of assessment to foresee (4C) treatment outcome. Factors that influence treatment response and determine prognosis need to be assessed in detail:

ÔCÕ: Characterize: clinical symptoms and subtype • Carefully characterize the symptom profile of depression noting, where possible, depressive subtype.

ÔCÕ: Calibrate: severity and chronicity • It is important to gauge the extent (severity) and duration (chronicity) of depression as these factors affect treatment choice and response ⁄ outcome. • Descriptors such as mild, moderate or severe are of limited value when used alone because they are poorly defined and difficult to apply with consistency. • Rating scales* should be used to quantify severity and can serve as a baseline measure to monitor future treatment response.

ÔCÕ: Corroborate: comorbidities and context • • • • •

If possible, obtain corroborative history. Identify medical and psychiatric comorbidities. Consider psychosocial context and factors contributing to illness (e.g. unresolved grief, domestic violence, unemployment and interpersonal relationship issues). Conduct physical examination and relevant medical investigations (e.g. thyroid levels). Past treatment history is an important guide to treatment choice and prognosis.

ÔCÕ: Consider: coping style and consequences • Identify adaptive factors such as personal strengths, support network, coping styles and willingness to engage in treatment. • Assess social and occupational functioning. If marked impairment is evident, seek a more detailed assessment by an occupational therapist and ⁄ or social worker. *Validated clinician-rated scales include Hamilton Depression Rating Scale (HAM-D) (30, 31), Montgomery–Asberg Depression Rating Scale (MADRS) (32) and the Inventory of Depressive Symptomatology (IDS) (33).

ÔPACEÕ: Treatment options for depression

The treatment options for depression include psychological interventions, pharmacotherapy and physical measures. Within these options, there are further treatment choices, and combinations of individual treatment can also be used. Therefore, potentially, there are a range of treatment options; however, in practice, a lack of 12

treatment specificity and differential efficacy limits treatment choice (34). By design, the acronym PACE sequences the treatment of depression and places a priority on psychological treatments. However, ultimately, treatment choice should be determined by factors such as availability, individual preference and effectiveness (see Box 4).

Depression CPR

Box 4. ÔPACEÕ: treatment options for depression The acronym ``PACE'' denotes the recommended treatment options for depression in the order they should be considered. However, treatment choice depends upon individual factors and treatment availability.

ÔPÕ: Psychological treatment (level I) • Consider psychological interventions especially if indicated by clinical features (e.g. presence of psychosocial issues, grief, loss and interpersonal problems). • Psychological therapies have efficacy comparable with antidepressant medications in the treatment of depression (12, 35, 36), where depressive features are not severe (HAM-D < 25), and there are no psychotic features (37). • There is a substantive evidence base for CBT (level I) (38–41), IPT (level I) (42, 43) and BAS (level I) (e.g. activity scheduling) (26, 27). Refer to Table 4 for summary of psychological therapies with levels I, II and III evidence in the treatment of major depression.

ÔAÕ: Antidepressant treatment (level I) ÔRATEÕ: When selecting an antidepressant consider: Risk, Adherence, Tolerability and Efficacy. ÔRÕ: Risk: TCAs and MAOIs are potentially lethal in overdose and can produce toxicity through interactions with other medications. SSRIs and other newer antidepressants can rarely cause serotonin syndrome and the risk of this should be considered (see Fig. 7 for antidepressant side-effect profile). ÔAÕ: Adherence: Adherence to the prescribed dose of antidepressant is essential. Dosing of medications should be as simple and convenient as possible in order to enhance adherence. Psychological engagement improves medication adherence. ÔTÕ: Tolerability: The side-effect profile of medications is a key determinant of antidepressant choice. Tolerability impacts upon adherence and outcome and should be routinely assessed. Common treatment side-effects should be discussed at the outset of treatment (see Fig. 7). ÔEÕ: Efficacy: Antidepressants may take up to 14 days to take effect but usually some improvement is discernible much earlier. Antidepressants are not addictive but abrupt cessation can precipitate withdrawal symptoms (especially with paroxetine, venlafaxine and TCAs). Therefore, when withdrawn, antidepressants should be tapered gradually. • SSRI (44–52). SSRIs are generally better tolerated than other classes of antidepressants and are suitable first-line. Sexual dysfunction and gastrointestinal symptoms are common. Many SSRIs (especially fluoxetine and paroxetine) cause significant CYP450 inhibition and care is needed when co-prescribed with other medications (53). • NARI (reboxetine) (54–56). Reboxetine is suitable first-line. Common side-effects include hypersomnia, fatigue and nausea. • NaSSA (mirtazapine) (57–60). Mirtazapine, a suitable first-line option, is associated with weight gain and drowsiness. • SNRI (venlafaxine, desvenlafaxine and duloxetine) (61). SNRIs appear to be more effective than SSRIs in treating severe depressive symptoms (HAM-D ‡25) and melancholia (62). In some cases, adverse effects may limit SNRIs to second-line treatment. However, if depression is severe (i.e. HAM-D >25), then SNRIs are a suitable first-line option. Sexual dysfunction and gastrointestinal symptoms are common with venlafaxine. • TCA (45–49, 63–65). In comparison with SSRIs, TCAs have a greater side-effect burden (anticholinergic and CNS) (66) and toxicity in overdose (53) and therefore are considered second-line. However, TCAs (especially those that have both noradrenergic and serotonergic activity such as amitriptyline and clomipramine) may be more effective when compared with other antidepressants in treating severe depressive symptoms (HAM-D ‡25), in particular patients with melancholia and those hospitalized because of severe depression (67–72). • MAOIs. Efficacious antidepressants but not recommended first-line because of risk of hypertensive crisis if necessary dietary and drug interaction restrictions are not adhered to (Fig. 3).

Clinical Utility of Antidepressants SSRIs NARIs NASSAs

First-line

SNRIs TCAs

Second-line

Legend Key to Figure

MAOIs

Acute efficacy

0

Tolerability difficulties

Fig. 3. Consideration of efficacy and tolerability for the principal antidepressant classes.†

ÔCÕ: Combining antidepressants and psychological therapies (level I) Consider psychological and antidepressant combination treatment if response to single modality has been suboptimal or failed, or if indicated by clinical features. • Combination therapies are more effective and reduce time to remission than either psychological or antidepressant treatment alone, especially in depression of moderate or greater severity (HAM-D ‡18) and chronic depression (level I) (36, 73–77).

ÔEÕ: ECT (level I) ECT is administered under general anaesthesia, either bilaterally or unilaterally, usually in an in-patient setting. The most common side-effect is cognitive impairment that is usually transient; however, there is also evidence that suggests some risk of longer term memory impairment (78, 79). • ECT is a safe and effective treatment (80–82), that is also effective when pharmacotherapy has failed (82, 83), although the risk of relapse remains. • Consider ECT if there is a high risk of suicide, greater severity, significant psychotic symptoms or if there has been a previous response to ECT treatment. † Many agents possess some degree of antidepressant properties and this list is not intended to be comprehensive. CBT, cognitive behavioural therapy; IPT, interpersonal therapy; BAS, behavioural activation strategies; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; SNRI, serotonin and noradrenaline reuptake inhibitor; NARI, noradrenaline reuptake inhibitor; NaSSA, noradrenaline and specific serotonergic antidepressant; MAOI, monoamine oxidase inhibitor; HAM-D, Hamilton rating scale for depression; ECT, electroconvulsive therapy.

13

Malhi et al. The above recommendations (PACE) apply to depressive disorders as defined by the signs and symptoms in Table 1. Typically, unipolar depression is a recurrent episodic illness that causes significant functional impairment. However, the latter can also be caused by subsyndromal depression, which subsumes admixtures of episodes that are brief (episodes of less than 2-week duration) and those marked by chronic symptoms of low intensity (dysthymia). Depression can therefore manifest with a variety of ÔsubthresholdÕ symptoms and such presentations can remain undetected and untreated because of comorbid anxiety or personality disorders. As such, subsyndromal depression is underresearched and it is difficult to make specific detailed recommendations.

in particular those with treatment implications are discussed briefly in Fig. 4 and Box 5. The precise criteria and treatment recommendations for atypical depression lack widespread consensus; however, in practice, ÔatypicalÕ features are not uncommon (see Box 5). In some contexts, and somewhat confusingly, ÔatypicalÕ is erroneously used to describe a depressive disorder with psychotic features. In these recommendations psychotic depression is used to refer to the occurrence of delusions and ⁄ or hallucinations (usually mood-congruent) within the context of a depressive disorder. Further, it is important to note that psychotic features confer a greater risk of suicide, and in this regard ECT may be considered first-line because of its greater efficacy in this ÔsubtypeÕ of depression (84, 85).

Depression subtypes

Other ÔsubtypesÕ of depression that have been identified with somewhat greater consistency, and

Box 5. Recommendations for specific depression subtypes Atypical features Characterized by mood reactivity and two or more of the following: significant weight gain or increased appetite, hypersomnia, leaden paralysis, long-standing pattern of sensitivity to interpersonal rejection (16). • SSRIs are considered preferable as first-line (level II) (86). • MAOIs appear to be more effective in this population (87) and can be considered in cases of non-response, but are not recommended as an initial option because of increased risk of adverse effects, contraindications and dietary restrictions (86). • Cognitive therapy has been demonstrated to be effective in atypical depression (level II) (88).

Melancholic features Melancholia is characterized by psychomotor changes and somatic symptoms (16). Melancholic depression has a lower placebo response rate compared with depression without melancholic features, suggesting lower rates of spontaneous recovery and a greater need for active treatment (89). • Evidence suggests that TCAs and dual acting agents have superior efficacy when compared with SSRIs (62, 67, 90, 91). • Depression with melancholic features appears to respond well to antidepressant and ECT treatment (80, 81). • Limited data report mixed findings in relation to efficacy of psychological treatments in depression with melancholic features (92, 93). Adjunctive psychological therapy may be of benefit for residual symptoms following an antidepressant response (refer to Box 7 ÔMaintenanceÕ section).

Psychotic features Describes depression accompanied by delusions and ⁄ or hallucinations that are usually, but not always, mood congruent (16). • TCAs appear to be more effective than other antidepressants in treating psychotic depression (94). • Combining an antidepressant with an antipsychotic may be more effective than an antidepressant alone; some but not all studies support the benefit of this combination (94). • Antipsychotic monotherapy is not as effective as a combination of antipsychotic and antidepressant (level I) (94). ECT is an effective alternative (84, 85). TCA, tricyclic antidepressant; SSRI, selective serotonin reuptake inhibitor; ECT, electroconvulsive therapy.

14

Depression CPR Summary of Recommendations Depression

Atypical features

Melancholic features

Psychotic features

Fig. 4. Summary of specific treatment recommendations for subtypes of depression. CBT, cognitive behavioural therapy; IPT, interpersonal therapy; ECT, electroconvulsive therapy; SSRI, selective serotonin reuptake inhibitor; SNRI, serotonin and noradrenaline reuptake inhibitor; MAOI, monoamine oxidase inhibitor; TCA, tricyclic antidepressant.

Continuation and maintenance treatment

Long-term continuing treatment gradually melds into maintenance. The return of depression prior to recovery is described as relapse, whereas thereafter it is termed recurrence. Having achieved recovery and

avoided relapse (see Box 6), it is important to sustain emotional and physical wellbeing and prevent the recurrence of depression (see Box 7). Integral to this process is a strong therapeutic relationship that facilitates engagement in treatment and permits ongoing monitoring and risk assessment.

Box 6. Continuation treatment General considerations • Following an initial response, treatment should be continued with a focus on stabilizing or achieving further improvement. • Combining psychological and pharmacological treatments improves clinical outcome and, during longer term treatment (>12 weeks), enhances adherence (75). • Planned follow-up should be scheduled with regular monitoring of side-effects and adjustment of treatment dosage as needed.

Continuing treatment • Evidence of an antidepressant effect is most likely to occur within the first 2 weeks of treatment (95–97). If no response occurs within this time period or if the patient fails to respond adequately within a reasonable time frame (up to 6 weeks), a treatment change is indicated. If remission is not achieved by 3 months, seek consultation or a second opinion and continue active treatment (level V). • Expert consensus recommends continuation of antidepressant treatment for at least 1 year following the onset of symptoms for an initial episode and 3 years for recurrent episodes (level V). If an initial episode included psychotic features, then continue treatment for at least 3 years (98). • If there are residual negative cognitions or relationship issues, consider psychological interventions such as CBT ⁄ IPT.

Risk of acute relapse: ROAR • Relapse rates are the highest immediately following remission and diminish with time (99). • The risk of relapse during the continuation phase of treatment is relatively high and is increased by a variety of factors (see Table 3). Table 3. Factors increasing the risk of acute relapse (ROAR) in depression ÔROARÕ risk factors (100–109) Concurrent factors Comorbid medical illness Life events ⁄ social stress Female gender Depressive episodes Greater number of prior episodes Longer duration of current episode

Symptoms Greater severity of depression Residual symptoms Presence of psychosis Outcome factors Treatment-resistance Residual symptoms

CBT, cognitive behavioural therapy; IPT, interpersonal therapy.

15

Malhi et al.

Box 7. Maintenance treatment General considerations • • • • •

Review with the patient, the benefits and burdens of maintaining ongoing treatment vs. the risk of recurrence. Work collaboratively to identify warning signs and develop a patient recovery ⁄ wellness plan to reduce risk factors for recurrence. Assist patient to identify and work towards their own recovery-based goals (level V). Re-evaluate treatment plans and address any comorbid conditions, psychosocial stressors (residual grief and loss) and functional impairment. Ensure proactive follow-up to detect recurrence of depressive symptoms.

Maintenance treatments Psychological • CBT has the largest evidence base in maintenance treatment. See Fig. 5 and Table 4 for an overview of evidence-based psychological therapies with potential specificity to phase of depression. • CBT can reduce the risk of relapse, with benefits sustained for several years beyond treatment (level II) (110–112). • IPT may be effective in those who have responded to acute IPT monotherapy (113). • MBCT has been effective in reducing relapse in patients with recurrent depression (level II) (114, 115).

Phases of Treatment

Acute

Continuation

Maintenance

MBCT CBT IPT BAS

Fig. 5. Schematic demonstrating the potential phase-specific application of psychological therapies with level I evidence.† See Table 4 for further details. † In the light of its phase-specific application, MBCT (level II) has also been included.

Psychosocial • Address psychosocial ⁄ lifestyle factors (accommodation, social support, employment). • Ensure social supports are in place or assist patient to link into support networks. • Consider occupational therapy or vocational support where there has been disengagement from activities.

Pharmacological • Antidepressant treatment diminishes the risk and severity of depressive relapse (116, 117); however, even with ongoing maintenance administration, recurrences may occur (118). • Lithium monotherapy is an effective alternative maintenance treatment option in unipolar depression (119) and may be considered if antidepressants cannot be tolerated (e.g. because of sexual dysfunction). However, long-term administration of lithium is associated with serious side-effects such as renal dysfunction (120) and therefore lithium levels should be closely monitored.

Maintaining antidepressant treatment • Maintain therapeutic dose that was effective during acute treatment because this dosage is generally more efficacious in preventing relapse or recurrence than lower Ômaintenance dosesÕ (121–124). • Assess and monitor for tolerability, adverse effects and adherence to treatment.

Stopping antidepressant treatment • Discontinuation symptoms may emerge following the cessation of all classes of antidepressants. Therefore, although the optimal regime remains unclear, antidepressant treatment should be discontinued gradually. • The risk of discontinuation symptoms is the greatest with higher doses of antidepressants and longer duration of treatment (up to 2 months); however, symptoms are usually transient and mild, and resolve with antidepressant reinstatement (125). • Amongst the antidepressants, discontinuation is more likely with venlafaxine (126, 127) and short-acting SSRIs (e.g. paroxetine) but less likely with fluoxetine (128, 129). • Abrupt cessation of TCAs may cause cholinergic-rebound phenomena (flu-like illness, myalgia and abdominal cramps).

ECT • There is limited evidence for long-term ECT treatment (130); however, maintenance ECT has been shown to be as effective as combined nortriptyline and lithium and superior to placebo in preventing relapse ⁄ recurrence (131, 132). • Review on an individual case-by-case basis and seek consultation (level V). BAS, behavioural activation strategies; IPT, interpersonal therapy; CBT, cognitive behavioural therapy; MBCT, mindfulness-based cognitive therapy; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; ECT, electroconvulsive therapy.

16

Depression CPR Table 4: Glossary of psychological therapies with level I–III evidence in depression

Therapy

Acute phase

Maintenance ⁄ relapse prevention

Cognitive Behavioural Therapy (CBT)

Level I (38–41)

Level II (110–112)

Interpersonal Therapy (IPT)

Level I (42, 43)

Level III (113)

Behavioural Activation Strategies (BAS)

Level I (26, 27)

–

Mindfulness-based Cognitive Therapy (MBCT)

–

Level II (114, 115)

Cognitive Behavioural Analysis System of Psychotherapy (CBASP)

Level II (133, 134)

Level III (135)

Internet-based Selfmanagement CBT

Level II (136)

–

Short-term Psychodynamic Psychotherapy

Level II (137).

–

Family Therapy

Level II (138–140)

–

Marital Therapy

Level II (141)

–

Basic principles

CBT employs a combination of cognitive and behavioural techniques to target maladaptive thinking, deficits and factors predisposing to and perpetuating depressed mood. IPT emphasizes the correlation between depression and the social environment. The therapy focuses on the current context and attempts to bring about active changes to help the individual to find solutions for, or adapt to, interpersonal problems. BAS strategies targets behaviours that maintain or worsen depression, particularly inertia and loss of pleasure and achievement. It involves, for example, scheduling activities and graded task assignments. MBCT differs from traditional CBT in that it does not focus on the content of thoughts. Rather, it emphasizes the process of attending to thoughts and feelings and experiencing and tolerating these without judgment. The focus of CBASP is to apply situational analysis techniques to social interactions and remedy the thought and behaviour patterns that lead to a disconnection between the patient and their environment. Thus far, therapy has been largely studied in patients with chronic depression. A structured treatment approach delivered online applying CBT principles with the aim of developing new types of behaviour and cognition. Can be delivered with or without therapist support (usually via online email or forum). Strategies include the use of the triangle of conflict (feelings, anxiety and defence) and the triangle of person (past, therapist and present). Short-term psychodynamic psychotherapy differs from longer term psychodynamic analysis in that it applies therapeutic focus, active therapist involvement and time restriction. Family therapy refers to a range of approaches including psychoeducational, systemic, behavioural and psychoanalytical models. Essentially, family therapy for depression aims to help family members disengage from destructive forms of communication, and through that process, reduce the symptoms of depression. Marital therapy, derived from social learning theory, aims to modify negative interactional behaviours between the couple and increase mutually supportive aspects of the relationship.

With respect to psychological interventions, it is important to consider the potential phase-specific benefits of individual therapies (see Fig. 5), noting, however, that, as yet, the evidence is incomplete and the findings from many studies are inconclusive. Further, to date, insufficient studies have been conducted to determine the specific benefits of psychological monotherapy vs. combination with medication. However, as regards IPT and CBT in combination with antidepressants, in addition to efficacy in the acute phase of treatment, these psychological interventions have been shown to facilitate remission and recovery and diminish the subsequent likelihood of relapse and recurrence (110– 113).

Managing partial or no response to treatment

The terms Ôtreatment resistantÕ, Ônon-responseÕ or Ôpartial response to treatmentÕ lack clear definition because varying criteria have been applied both clinically and in depression research to define degrees of response (142). In general, these terms are used to describe an inadequate response to appropriate therapeutic measures for depression that can include medications and ⁄ or psychological interventions and ⁄ or physical treatments. The difficulty in operationalizing these definitions is immediately evident. Deciding on what is an appropriate therapy, and the context within which it should be administered, requires a much better understanding of treatment response in depression. Expert consensus has also not been achievable because of disagreement as to the adequacy of dose and

duration of pharmacotherapy and the relative importance of psychological and pharmacological strategies (143–145). In practice, partial or non-response to treatment is experienced by the individual as ongoing depressive symptoms and a lack of functional recovery. Generally, with each treatment failure the likelihood of a subsequent response decreases and the chance of eventual remission and recovery diminishes (109). A discernible improvement in response to medication usually becomes evident within the first 2 weeks of treatment (95–97) and a measurable change within this time frame is more likely to result in a sustained response (146, 147). However, a lack of continuing improvement beyond the first few weeks of treatment is likely to result in longer term nonresponse (148, 149). 17

Malhi et al. Therefore, the practical treatment of partial or no treatment response requires experience and careful consideration. Specifically, this entails the

integration of clinical management skills and therapeutic strategies. The key elements of these are outlined in Box 8.

Box 8. Managing partial or no treatment response

Review adherence & dose Seek consultation Re-evaluate diagnosis

Optimise

Clinical Management

ECT Re-assess for comorbidities

Therapeutic Strategies

Substitute

Augment/ Combine

Fig. 6. Managing partial or no treatment response.

Clinical management Review adherence and dosage. Ensure adherence to and satisfaction with treatment plan. If taking an antidepressant review dosage (Fig. 6). Re-evaluate diagnosis. Consider maintaining factors of depression, such as psychosocial stressors. Re-evaluate substance abuse or personality issues and re-consider alternative causes (e.g. bipolar disorder and thyroid dysregulation). Re-assess comorbidities. Especially anxiety, drug and alcohol, or personality disorders. Assess for medical comorbidities. Refer and consult. Consultation with colleagues or referral to a specialist or specialist clinic should be considered in complex cases, or where there has been partial or no response to multiple treatment trials. Advice should also be sought when prescribing novel treatments. In conjunction with clinical management, structured rating scales (see ÔAssessmentÕ) can assist in quantifying treatment response and determining change in clinical profile.

Therapeutic strategies Optimize • Optimize existing treatments. • If taking an antidepressant, optimize dose (where possible, e.g. TCAs, check levels). • TCAs, venlafaxine and escitalopram generally have antidepressant activity across a broader dose range (150–152).

Augment and ⁄ or combine • Add psychological treatment (CBT) or antidepressant medication as indicated ⁄ necessary. • Pharmacological augmentation strategies: lithium (level I) (153, 154), atypical antipsychotics (level I) (olanzapine, risperidone, quetiapine) (155), short-term benzodiazepine use (level I) (156) or thyroid hormone (157, 158). Note, lithium is used widely as an augmentation agent and can be administered in conjunction with all antidepressants. • Combining antidepressants: there is little controlled evidence to support this approach, but clinically it is occasionally used to treat non-response. Logical combinations include combining serotonergic and noradrenergic acting drugs (159–161). • Caution: when employing augmentation strategies or if combining antidepressants, monitor carefully for side-effects and potential toxicity.

Substitute Includes changing between antidepressants and psychological treatments, or substituting class of antidepressant. • Before altering any treatment, allow a trial of appropriate duration, usually 2–6 weeks, at adequate dosage for pharmacological or psychological treatments (sometimes longer) (162, 163) (see also Box 6). • When substituting antidepressants, alter antidepressant class unless reason for substitution is poor tolerability, which has prevented an adequate trial. • Consider dual-acting agents (e.g. venlafaxine and duloxetine) (164), TCAs (165) or MAOI (e.g. phenelzine) if adverse effects and dietary restrictions can be tolerated (109).

ECT (level II) • ECT is an effective alternative treatment option in cases of marked severity, risk or ongoing non-response to medication or psychological treatments (80–82). TCA, tricyclic antidepressant; CBT, cognitive behavioural therapy; MAOI, monamine oxidase inhibitor; ECT, electroconvulsive therapy.

Discussion

The management of depression, even that which is uncomplicated by comorbidity, is a sophisticated process. Throughout the Depression CPR, management advice has been balanced so as to incor18

porate both clinical experience and evidence-based findings. The importance of the individual and the need to form a therapeutic alliance have been emphasized throughout and psychological approaches have been given primacy. While the focus of the Depression CPR is to guide the

Depression CPR management of depression in adults, clinical depression arises in other populations and often in conjunction with other illnesses. These specific circumstances, along with antidepressant sideeffects and novel ⁄ emerging treatments, are briefly addressed.

use the Depression CPR in conjunction with publications that outline the evidence for managing depression with comorbid anxiety (173), substance misuse (174, 175), personality disorders (176), schizophrenia (177) and medical problems (178, 179).

Special populations and comorbidities

Antidepressant side-effects and novel treatments

The Depression CPR target the management of depression in adults because this is the population that provides the majority of the evidence base. The recommendations have therefore not reviewed the evidence for special populations. However, the reader is directed to existing publications that provide specific guidance in managing depression in young people (166, 167), the elderly (168, 169) and during the perinatal period (170–172). In practice, depression is often accompanied by other disorders and this necessarily complicates its management. However, because of insufficient evidence it is not yet possible to develop recommendations that address the many varied presentations of clinical depression. To deal with such complex presentations the reader is encouraged to

Antidepressants can produce a vast range of sideeffects and for specific information recognized pharmaceutical data sources and the product information of an individual agent should be consulted. Class effects are summarized in Fig. 7, but a detailed description is beyond the scope of the Depression CPR. Similarly, it has not been possible to accommodate in the Depression CPR detailed discussion of the many novel treatments for depression for which there is accumulating evidence. For example, St JohnÕs wort (180), meditation (181), exercise (182), innovative pharmacological agents [e.g. agomelatine (183)] and a range of physical interventions [for example, vagal nerve stimulation, transcranial magnetic stimulation, deep brain stim-

Side effects associated with the principle antidepressant classes

Fig. 7. Side-effects associated with the principle antidepressant classes. Source: adapted from Refs (191–193).  MAOIs require dietary restrictions to prevent hypertensive crisis, some combinations with other drugs can be fatal. +, uncommon; ++, common; +++, very common; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; SNRI, serotonin and noradrenaline reuptake inhibitor; NARI, noradrenaline reuptake inhibitor; NaSSA, noradrenaline and specific serotonergic antidepressant; MAOI, monoamine oxidase inhibitor; RIMA, reversible inhibitor of monoamine oxidase. Antidepressants are generally well-tolerated and are not addictive, but non-compliance or discontinuation because of adverse effects remains a significant problem in clinical settings and research trials. The figure outlines the main adverse effects experienced, according to each antidepressant class. Compared with other antidepressants, SSRIs tend to be safer and better tolerated by patients, with a more favourable adverse effect profile, even at high doses (68). Many of the adverse effects of SSRIs, such as gastrointestinal symptoms, tend to be transient and cease within a few days or weeks after commencing treatment (194). Tricyclic antidepressants have higher discontinuation rates than SSRIs (191), are associated with greater rates of anticholinergic side-effects, hypotensive and sedation effects and can also be toxic in overdose (194). The sideeffect and safety profile of TCAs limits their use as a first-line treatment option. Similarly, MAOIs are not favoured as initial treatment options because of the risk of hypertensive crisis if strict dietary requirements are not maintained (195). The blood levels of some antidepressants (e.g. TCAs) can be monitored, but this is not usually necessary and is not routinely advocated.

19

Malhi et al. ulation (184–187) and light therapy (188–190)], all of which are increasingly used worldwide in the treatment of mood disorders. To conclude, the imprecision with which depression has been defined has limited research and understanding of the disorder and thereby constricted the sophistication with which it is routinely managed. The Depression CPR have been developed to provide basic practical guidance as to the management of depression and are a combination of datadriven evidence and clinical experience. They cannot take into account the myriad of clinical variables that are invariably present, and are thus not prescriptive, and need to be used flexibly. Recommendations, like guidelines, are practical clinical tools, derived from an incomplete and evolving database. They need to be interpreted taking into account the personÕs clinical circumstances, sociocultural context, comorbidities and local health resources. Therefore, they do not represent a reference standard of care in medicolegal proceedings. The recommendations have been constructed so as to provide a useful framework for the clinical management of depression and should ideally be used in conjunction with other recognized sources of information (72, 191, 192, 196) and the application of clinical wisdom.

sory boards, received funding for research and has been in receipt of honoraria for talks at sponsored meetings worldwide involving the following companies: AstraZeneca, Eli Lilly, Jansen-Cilag, Organon, Pfizer and Wyeth. Professor Garry Walter has received educational grants from Eli Lilly, Janssen-Cilag and Pfizer, a research grant from AstraZeneca, and travel assistance and an honorarium for a talk from Eli Lilly. Dr Lisa Lampe has received honoraria for lectures, workshops, advisory boards and educational material in the past 5 years from the following companies: Wyeth, Lundbeck, Pfizer, Sanofi, Janssen Cilag and AstraZeneca. She has received travel assistance from Wyeth and sits on the Pristiq Advisory Board (Wyeth). In the last 5 years Professor Richard Porter has received honoraria for speaking engagements from Janssen-Cilag and Sanofi-Aventis. During the past 3 years, Professor Roger Mulder received honoraria for speaking and travel assistance from Douglas Pharmaceuticals, Janssen-Cilag and AstraZeneca. Professor Michael Berk has received funding for research from Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Organon, Novartis, Mayne Pharma, Servier, AstraZeneca, has received honoraria for speaking engagements from AstraZeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Organon, Pfizer, Sanofi Synthelabo, Solvay, Wyeth and served as a consultant to AstraZeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck and Pfizer. Danielle Adams, Andrea Taylor, Dr Nick OÕConnor, Dr Michael Paton, Dr Liz Newton and Dr Ann Wignall have no competing interests.

References Acknowledgements This paper was part of a larger project, Mood Matters, which represented a collaboration between the Northern Sydney Central Coast Mental Health Drug & Alcohol (NSCCMHDA), NSW Health Clinical Redesign Program and the CADE Clinic, University of Sydney. The authors sincerely acknowledge contributions by Dr Nick Kowalenko, Dr Glenys Dore, Dr Kevin Vaughan, Rosa Portus, Dr Peter Short and Vicki Campbell. The authors also acknowledge all staff and consumers of NSCCMHDA who actively participated in this project and particularly the members of the multidisciplinary advisory panel who participated in the development process of these practice recommendations. Prof Gin Malhi acknowledges the NHMRC Program Grant (510135) for essential financial support. This publication has been made possible through infrastructure support from NSCCMHDA and the University of Sydney CADE Clinic and an unrestricted educational grant from Servier. The icons used in this article have been sourced from Clip Art, Microsoft Office Online (http://office.microsoft.com/enau/clipart/default.aspx) and used in accordance with the Microsoft Service Agreement. The media elements are intended to enhance the existing content and are not considered to be the primary value of the recommendations.

Declaration of interest In the past 3 years, Professor Gin Malhi has served on a number of international and national pharmaceutical advi-

20

1. Ustun TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJL. Global burden of depressive disorders in the year 2000+. Br J Psychiatry 2004;184:386–392. 2. World Health Organisation. The ICD-10 classification of mental and behavioural disorders: clinical description and diagnostic guidelines. Geneva: WHO, 1992. 3. Schoevers R, Henricus L, Koppelmans V, Kool S, Dekker J. Managing the patient with co-morbid depression and an anxiety disorder. Drugs 2008;68:1621–1634. 4. Ustun TB. Cross-national epidemiology of depression and gender. J Gend Specif Med 2000;3:54–58. 5. Jenkins R, Lewis G, Bebbington P et al. The National Psychiatric Morbidity Surveys of Great Britain-initial findings from the Household Survey. Psychol Med 2000;27:775–789. 6. Alonso J, Angermeyer MC, Bernert S et al. Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl 2004; 109 (Suppl. 420):21–27. 7. Kessler RC, Berglund P, Demler O et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003;289:3095–3105. 8. Inskip HM, Harris EC, Barraclough B. Lifetime risk of suicide for affective disorder, alcoholism and schizophrenia. Br J Psychiatry 1998;172:35–37. 9. Eaton WW, Shao H, Nestadt G, Lee BH, Bienvenu OJ, Zandi P. Population-based study of first onset and chronicity in major depressive disorder. Arch Gen Psychiatry 2008;65:513–520.

Depression CPR 10. Lee AS, Murray RM. The long-term outcome of Maudsley depressives. Br J Psychiatry 1988;153:741–751. 11. Khan A, Redding N, Brown WA. The persistence of the placebo response in antidepressant clinical trials. J Psychiatr Res 2008;42:791–796. 12. Casacalenda N, Perry JC, Looper K. Remission in major depressive disorder: a comparison of pharmacotherapy, psychotherapy, and control conditions. Am J Psychiatry 2002;159:1354–1360. 13. Keller MB, Lavori PW, Mueller TI et al. Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects. Arch Gen Psychiatry 1992;49:809–816. 14. Malhi G, Parker G, Greenwood J. Structural and functional models of depression: from sub-types to substrates. Acta Psychiatr Scand 2005;111:94–105. 15. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron 2002;34:13–25. 16. American Psychiatric Association. Diagnostic and statistical manual for mental disorders, 4th edn. text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association, 2000. 17. Muller MJ, Himmerich H, Kienzle B, Szegedi A. Differentiating moderate and severe depression using the Montgomery–Asberg depression rating scale (MADRS). J Affect Disord 2003;77:255–260. 18. Ballesteros J, Bobes J, Bulbena A et al. Sensitivity to change, discriminative performance, and cutoff criteria to define remission for embedded short scales of the Hamilton depression rating scale (HAMD). J Affect Disord 2007;102:93–99. 19. Kupfer D. Long-term treatment of depression. J Clin Psychiatry 1991;52 (Suppl. 5):28–34. 20. Malhi GS, Adams D. Are Guidelines in need of CPR? The Development of Clinical Practice Recommendations (CPR) for Mood Disorders. Acta Psychiatr Scand 2009;119 (Suppl. 439):5–7. 21. National Health and Medical Research Council. A guide to the development, implementation and evaluation of clinical practice guidelines. Canberra: Commonwealth of Australia, 1998. 22. Bradvik L, Mattisson C, Bogren M, Nettelbladt P. Longterm suicide risk of depression in the Lundby cohort 1947–1997 – severity and gender. Acta Psychiatr Scand 2008;117:185–191. 23. Mynors-Wallis LM, Gath DH, Day A, Baker F. Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care. Br Med J 2002;320:26– 30. 24. Dowrick C, Dunn G, Ayuso-Mateos JL et al. Problem solving treatment and group psychoeducation for depression: Multicentre randomised controlled trial. Br Med J 2000;321:1450–1454. 25. Cuijpers P, van Straten A, Warmerdam L. Problem solving therapies for depression: a meta-analysis. Eur Psychiatry 2007;22:9–15. 26. Cuijpers P, van Straten A, Wamerdam l. Behavioural activation treatments of depression: a meta-analysis. Clin Psychol Rev 2007;27:318–326. 27. Ekers D, Richards D, Gilbody S. A meta-analysis of randomized trials of behavioural treatment of depression. Psychol Med 2008;38:611–623. 28. Dimidjian S, Hollon SD, Dobson KS et al. Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of

29.

30.

31. 32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

42.

43.

44.

45.

adults with major depression. J Consult Clin Psychol 2006;74:658–670. Meyer B, Pilkonis PA, Krupnick JL, Egan MK, Simmens SJ, Sotsky SM. Treatment expectancies, patient alliance, and outcome: further analyses from the National Institute of Mental Health Treatment of Depression Collaborative Research Program. J Consult Clin Psychol 2002;70:1051– 1055. Hamilton M. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychopharmacol 1967;6:278–296. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56–62. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382–389. Trivedi MH, Rush AJ, Ibrahim HM et al. The Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) and Self-Report (IDS-SR), and the Quick Inventory of Depressive Symptomatology, Clinician Rating (QIDS-C) and Self-Report (QIDS-SR) in public sector patients with mood disorders: a psychometric evaluation. Psychol Med 2004;34:73–82. Gartlehner G, Gaynes BN, Hansen RA et al. Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians. Ann Intern Med 2008;149:734–750. Elkin I, Shea MT, Watkins JT et al. National Institute of Mental Health Treatment of Depression Collaborative Research Program. General effectiveness of treatments. Arch Gen Psychiatry 1989;46:971–982. De Maat SM, Dekker J, Schoevers RA, De Jonghe F. Relative efficacy of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis. Psychother Res 2006;16:566–578. Haby MM, Donnelly M, Corry J, Vos T. Cognitive behavioural therapy for depression, panic disorder and generalized anxiety disorder: a meta-regression of factors that may predict outcome. Aust NZ J Psychiatry 2006;40:9–19. DeRubeis RJ, Gelfand LA, Tang TZ, Simons AD. Medications versus cognitive behaviour therapy for severely depressed outpatients: meta-analysis of four randomized comparisons. Am J Psychiatry 1999;156:1007–1013. Gloaguen V, Cottraux J, Cucherat M, Blackburn I-M. A meta-analysis of the effects of cognitive therapy in depressed patients. J Affect Disord 1998;49:59–72. Dobson KS. A meta-analysis of the efficacy of cognitive therapy for depression. J Consult Clin Psychol 1989;57:414–419. Butler AC, Chapman JE, Forman EM, Beck AT. The empirical status of cognitive-behavioral therapy: a review of meta-analyses. Clin Psychol Rev 2006;26:17–31. de Mello MF, de Jesus Mari J, Bacaltchuk J, Verdeli H, Neugebauer R. A systematic review of research findings on the efficacy of interpersonal therapy for depressive disorders. Eur Arch Psychiatry Clin Neurosci 2005;255:75–82. Jarrett RB, Rush AJ. Short-term psychotherapy of depressive disorders: current status and future directions. Psychiatry 1994;57:115. Katzman MA, Tricco AC, McIntosh D et al. Paroxetine versus placebo and other agents for depressive disorders: a systematic review and meta-analysis. J Clin Psychiatry 2007;68:1845–1859. Stark P, Hardison CD. A review of multicenter controlled studies of fluoxetine vs. imipramine and placebo in out-

21

Malhi et al.

46.

47.

48.

49.

50.

51.

52.

53.

54.

55.

56.

57.

58.

59.

60.

61.

22

patients with major depressive disorder. J Clin Psychiatry 1985;46(3 Pt 2):53–58. Feighner JP, Boyer WF. Paroxetine in the treatment of depression: a comparison with imipramine and placebo. Acta Psychiatr Scand Suppl 1989;350:125–129. Lydiard RB, Laird LK, Morton WA Jr et al. Fluvoxamine, imipramine, and placebo in the treatment of depressed outpatients: effects on depression. Psychopharmacol Bull 1989;25:68–70. Reimherr FW, Chouinard G, Cohn CK et al. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. J Clin Psychiatry 1990;51(suppl. B):18–27. Doogan DP, Langdon CJ. A double-blind, placebo-controlled comparison of sertraline and dothiepin in the treatment of major depression in general practice. Int Clin Psychopharmacol 1994;9:95–100. Muijen M, Roy D, Silverstone T, Mehmet A, Christie M. A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients. Acta Psychiatr Scand 1988;78:384–390. Kiev A. A double-blind, placebo-controlled study of paroxetine in depressed outpatients. J Clin Psychiatry 1992;53(suppl.):27–29. Heiligenstein JH, Tollefson GD, Faries DE. A double-blind trial of fluoxetine, 20 mg, and placebo in out-patients with DSM-III-R major depression and melancholia. Int Clin Psychopharmacol 1993;8:247–251. Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol 2007;151:737–748. Versiani MMD, Amin MMF, Chouinard GMFF. Doubleblind, placebo-controlled study with reboxetine in inpatients with severe major depressive disorder. J Clin Psychopharmacol 2000;20:28–34. Andreoli V, Caillard V, Deo RS, Rybakowski JK, Versiani M. Reboxetine, a new noradrenaline selective antidepressant, is at least as effective as fluoxetine in the treatment of depression. J Clin Psychopharmacol 2002; 22:393–399. Papakostas GI, Nelson JC, Kasper S, Moller HJ. A metaanalysis of clinical trials comparing reboxetine, a norepinephrine reuptake inhibitor, with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. Eur Neuropsychopharmacol 2008;18:122–127. Anttila SA, Leinonen EV. A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev 2001;7:249–264. Amini H, Aghayan S, Jalili SA, Akhondzadeh S, Yahyazadeh O, Pakravan-Nejad M. Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a double-blind, randomized trial. J Clin Pharm Ther 2005;30:133–138. Leinonen E, Skarstein J, Behnke K, Agren H, Helsdingen J, The Nordic Antidepressant Study G. Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Int Clin Psychopharmacol 1999;14:329–337. Benkert O, Szegedi A, Kohnen R. Mirtazapine compared with paroxetine in major depression. J Clin Psychiatry 2000;61:656–663. Papakostas GI, Thase ME, Fava M, Nelson JC, Shelton RC. Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of

62.

63.

64.

65.

66. 67.

68.

69.

70.

71.

72.

73.

74.

75.

76.

77.

studies of newer agents. Biol Psychiatry 2007;62:1217– 1227. Tzanakaki M, Guazzelli M, Nimatoudis I, Zissis NP, Smeraldi E, Rizzo F. Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia. Int Clin Psychopharmacol 2000;15:29–34. Rickels K, Schweizer E, Clary C, Fox I, Weise C. Nefazodone and imipramine in major depression: a placebo-controlled trial. Br J Psychiatry 1994;164:802– 805. Fabre L, Birkhimer LJ, Zaborny BA, Wong LF, Kapik BM. Fluvoxamine versus imipramine and placebo: a doubleblind comparison in depressed patients. Int Clin Psychopharmacol 1996;11:119–127. Cohn CK, Robinson DS, Roberts DL, Schwiderski UE, OÕBrien K, Ieni JR. Responders to antidepressant drug treatment: a study comparing nefazodone, imipramine, and placebo in patients with major depression. J Clin Psychiatry 1996;57(suppl. 2):15–18. Guaiana G, Barbui C, Hotopf M. Amitriptyline for depression. Cochrane Database Syst Rev 2007:3: CD004186. Perry PJ. Pharmacotherapy for major depression with melancholic features: relative efficacy of tricyclic versus selective serotonin reuptake inhibitor antidepressants. J Affect Disord 1996;39:1–6. Anderson IM. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord 2000;58:19–36. Danish University Antidepressant Group. Citalopram: clinical effect profile in comparison with clomipramine. A controlled multicenter study. Psychopharmacology 1986;90:131–138. Danish University Antidepressant Group. Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. J Affect Disord 1990;18:289–299. Danish University Antidepressant Group. Moclobemide: a reversible MAO-A-inhibitor showing weaker antidepressant effect than clomipramine in a controlled multicenter study. J Affect Disord 1993;28:105–116. Anderson IM, Ferrier IN, Baldwin RC et al. Evidencebased guidelines for treating depressive disorders with antidepressants: a revision of the 2000 British Association for Psychopharmacology guidelines. J Psychopharmacol 2008;22:343–396. Schramm E, Schneider D, Zobel I et al. Efficacy of interpersonal psychotherapy plus pharmacotherapy in chronically depressed inpatients. J Affect Disord 2008;109:65–73. Schramm E, van Calker D, Dykierek P et al. An intensive treatment program of interpersonal psychotherapy plus pharmacotherapy for depressed inpatients: acute and long-term results. Am J Psychiatry 2007;164:768–777. Pampallona S, Bollini P, Tibaldi G, Kupelnick B, Munizza C. Combined pharmacotherapy and psychological treatment for depression: a systematic review. Arch Gen Psychiatry 2004;61:714–719. Simon J, Pilling S, Burbeck R, Goldberg D. Treatment options in moderate and severe depression: decision analysis supporting a clinical guideline. Br J Psychiatry 2006;189:494–501. Manber R, Kraemer HC, Arnow BA et al. Faster remission of chronic depression with combined psychotherapy and medication than with each therapy alone. J Consult Clin Psychol 2008;76:459–467.

Depression CPR 78. Sackeim HA, Prudic J, Fuller R, Keilp J, Lavori PW, Olfson M. The cognitive effects of electroconvulsive therapy in community settings. Neuropsychopharmacology 2007; 32:244–254. 79. Rose D, Fleischmann P, Wykes T, Leese M, Bindman J. PatientsÕ perspectives on electroconvulsive therapy: systematic review. Br Med J 2003;326:1363. 80. Pagnin D, Queiroz V, Pini S, Cassano GB. Efficacy of ECT in depression: a meta-analytic review. J ECT 2004;20:13– 20. 81. Lisanby SH. Electroconvulsive therapy for depression. N Engl J Med 2007;357:1939–1945. 82. UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003;361:799–808. 83. National Institute for Health and Clinical Excellence. Depression: management of depression in primary and secondary care: clinical Guideline 23. London: NHS, 2004. 84. Coryell W. The treatment of psychotic depression. J Clin Psychiatry 1998;59(suppl. 1):22–27; discussion 8-9. 85. Kho KH, van Vreeswijk MF, Simpson S, Zwinderman AH. A meta-analysis of electroconvulsive therapy efficacy in depression. J ECT 2003;19:139–147. 86. Ayuso-Gutierrez JL. Depressive subtypes and efficacy of antidepressive pharmacotherapy. World J Biol Psychiatry 2005;6(4 supp 2):31–37. 87. Henkel V, Mergl R, Allgaier A-K, Kohnen R, Mo¨ller H-J, Hegerl U. Treatment of depression with atypical features: a meta-analytic approach. Psychiatry Res 2006;141:89–101. 88. Jarrett RB, Schaffer M, McIntire D, Witt-Browder A, Kraft D, Risser RC. Treatment of atypical depression with cognitive therapy or phenelzine: a double-blind, placebo-controlled trial. Arch Gen Psychiatry, 1999;56:431–437. 89. Brown WA. Treatment response in melancholia. Acta Psychiatr Scand 2007;115(s433):125–129. 90. Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001;178:234– 241. 91. Smith D, Dempster C, Glanville J, Freemantle N, Anderson I. Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Br J Psychiatry 2002;180:396– 404. 92. Thase ME, Friedman ES. Is psychotherapy an effective treatment for melancholia and other severe depressive states? J Affect Disord 1999;54:1–19. 93. Luty SE, Carter JD, McKenzie JM et al. Randomised controlled trial of interpersonal psychotherapy and cognitive-behavioural therapy for depression. Br J Psychiatry 2007;190:496–502. 94. Wijkstra J, Lijmer J, Balk FJ, Geddes JR, Nolen WA. Pharmacological treatment for unipolar psychotic depression: systematic review and meta-analysis. Br J Psychiatry, 2006;188:410–415. 95. Stassen HH, Angst J, Delini-Stula A. Fluoxetine versus moclobemide: cross-comparison between the time courses of improvement. Pharmacopsychiatry 1999;32:56–60. 96. Stassen HH, Kuny S, Hell D. The speech analysis approach to determining onset of improvement under antidepressants. Eur Neuropsychopharmacol 1998;8:303– 310. 97. Posternak MA, Zimmerman M. Is there a delay in the antidepressant effect? A meta-analysis. J Clin Psychiatry 2005;66:148–158.

98. Viguera AC, Baldessarini RJ, Friedberg J. Discontinuing antidepressant treatment in major depression. Harv Rev Psychiatry 1998;5:293–306. 99. Belsher G, Costello CG. Relapse after recovery from unipolar depression: a critical review. Psychol Bull 1988;104:84–96. 100. Dombrovski AY, Mulsant BH, Houck PR et al. Residual symptoms and recurrence during maintenance treatment of late-life depression. J Affect Disord 2007;103:77–82. 101. Reynolds CF III, Dew MA, Pollock BG et al. Maintenance treatment of major depression in old age. N Engl J Med 2006;354:1130–1138. 102. Iosifescu DV, Nierenberg AA, Alpert JE et al. Comorbid medical illness and relapse of major depressive disorder in the continuation phase of treatment. Psychosomatics 2004;45:419–425. 103. Kanai T, Takeuchi H, Furukawa TA et al. Time to recurrence after recovery from major depressive episodes and its predictors. Psychol Med 2003;33:839–845. 104. McGrath PJ, Stewart JW, Quitkin FM et al. Predictors of relapse in a prospective study of fluoxetine treatment of major depression. Am J Psychiatry 2006;163:1542–1548. 105. Kessing LV, Andersen PK. Predictive effects of previous episodes on the risk of recurrence in depressive and bipolar disorders. Curr Psychiatry Rep 2005;7:413– 420. 106. Dotoli D, Spagnolo C, Bongiorno F et al. Relapse during a 6-month continuation treatment with fluvoxamine in an Italian population: the role of clinical, psychosocial and genetic variables. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:442–448. 107. Ramana R, Paykel ES, Cooper Z, Hayhurst H, Saxty M, Surtees PG. Remission and relapse in major depression: a two-year prospective follow-up study. Psychol Med 1995;25:1161–1170. 108. Kessing LV. Subtypes of depressive episodes according to ICD-10: prediction of risk of relapse and suicide. Psychopathology 2003;36:285–291. 109. Rush AJ, Trivedi MH, Wisniewski SR et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006;163:1905–1917. 110. Hollon SD, DeRubeis RJ, Shelton RC et al. Prevention of relapse following cognitive therapy vs medications in moderate to severe depression. Arch Gen Psychiatry, 2005;62:417–422. 111. Paykel ES, Scott J, Cornwall PL et al. Duration of relapse prevention after cognitive therapy in residual depression: follow-up of controlled trial. Psychol Med 2005;35:59–68. 112. Bockting CLH, Schene AH, Spinhoven P et al. Preventing relapse ⁄ recurrence in recurrent depression with cognitive therapy: a randomized controlled trial. J Consult Clin Psychol 2005;73:647–657. 113. Frank E, Kupfer DJ, Buysse DJ et al. Randomized trial of weekly, twice-monthly, and monthly interpersonal psychotherapy as maintenance treatment for women with recurrent depression. Am J Psychiatry 2007;164:761– 767. 114. Teasdale JD, Segal ZV, Williams JMG, Ridgeway VA, Soulsby JM, Lau MA. Prevention of relapse ⁄ recurrence in major depression by mindfulness-based cognitive therapy. J Consult Clin Psychol 2000;68:615–623. 115. Ma SH, Teasdale JD. Mindfulness-based cognitive therapy for depression: replication and exploration of differential relapse prevention effects. J Consult Clin Psychol 2004;72:31–40.

23

Malhi et al. 116. Katon W, Rutter C, Ludman EJ et al. A randomized trial of relapse prevention of depression in primary care. Arch Gen Psychiatry 2001;58:241–247. 117. Akerblad AC, Bengtsson F, von Knorring L, Ekselius L. Response, remission and relapse in relation to adherence in primary care treatment of depression: a 2-year outcome study. Int Clin Psychopharmacol 2006;21:117–124. 118. Byrne SE, Rothschild AJ. Loss of antidepressant efficacy during maintenance therapy: possible mechanisms and treatments. J Clin Psychiatry 1998;59:279–288. 119. Cipriani A, Smith K, Burgess S, Carney S, Goodwin G, Geddes J. Lithium versus antidepressants in the long-term treatment of unipolar affective disorder. Cochrane Database Syst Rev 2006;4:CD003492. 120. van Gerven HA, Boer WH. Chronic renal function disorders during lithium use. Ned Tijdschr Geneeskd 2006;150:1715–1718. 121. Thase ME. Preventing relapse and recurrence of depression: a brief review of therapeutic options. CNS Spectr 2006;11(12 suppl. 15):12–21. 122. Reynolds CF III, Perel JM, Frank E et al. Three-year outcomes of maintenance nortriptyline treatment in latelife depression: a study of two fixed plasma levels. Am J Psychiatry 1999;156:1177–1181. 123. Dawson R, Lavori PW, Coryell WH, Endicott J, Keller MB. Maintenance strategies for unipolar depression: an observational study of levels of treatment and recurrence. J Affect Disord 1998;49:31–44. 124. Miklowitz DJ, George EL, Richards JA, Simoneau TL, Suddath RL. A randomized study of family-focused psychoeducation and pharmacotherapy in the outpatient management of bipolar disorder. Arch Gen Psychiatry 2003;60:904–912. 125. Perahia DG, Kajdasz DK, Desaiah D, Haddad PM. Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder. J Affect Disord 2005;89:207–212. 126. Tint A, Haddad PM, Anderson IM. The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: a randomised study. J Psychopharmacol 2008;22:330–332. 127. Haddad PM, Anderson IM. Recognising and managing antidepressant discontinuation symptoms. Adv Psychiatr Treat, 2007;13:447–457. 128. Schatzberg AF, Blier P, Delgado PL, Fava M, Haddad PM, Shelton RC. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research. J Clin Psychiatry 2006;67(suppl. 4):27–30. 129. Michelson D, Fava M, Amsterdam J et al. Interruption of selective serotonin reuptake inhibitor treatment. Doubleblind, placebo-controlled trial. Br J Psychiatry 2000;176:363–368. 130. Frederikse MMD, Petrides GMD, Kellner CMD. Continuation and maintenance electroconvulsive therapy for the treatment of depressive illness: a response to the National Institute for Clinical Excellence report. J ECT 2006;22:13–17. 131. Kellner CH, Knapp RG, Petrides G et al. Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry 2006;63:1337–1344. 132. Gagne GG Jr, Furman MJ, Carpenter LL, Price LH. Efficacy of continuation ECT and antidepressant drugs compared to long-term antidepressants alone in depressed patients. Am J Psychiatry 2000;157:1960–1965.

24

133. Keller MB, McCullough JP, Klein DN et al. A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med, 2000;342:1462–1470. 134. Schatzberg AF, Rush AJ, Arnow BA et al. Chronic depression: medication (nefazodone) or psychotherapy (CBASP) is effective when the other is not. Arch Gen Psychiatry 2005;62:513–520. 135. Klein DN, Santiago NJ, Vivian D et al. Cognitive-behavioral analysis system of psychotherapy as a maintenance treatment for chronic depression. J Consult Clin Psychol 2004;72:681–688. 136. Spek V, Cuijers P, Nyki ek I, Keyzer J, Pop V. Internetbased cognitive behaviour therapy for symptoms of depression and anxiety: a meta-analysis. Psychol Med 2007;37:319–328. 137. Abbass AA, Hancock JT, Henderson J, Kisely S. Short-term psychodynamic psychotherapies for common mental disorders. Cochrane Database Syst Rev 2006; 4: CD004687. 138. Henken HT, H MJH, Churchill R, Restifo K, Roelofs J. Family therapy for depression. Cochrane Database Syst Rev 2007; 3: CD006728. 139. Diamond GS, Reis BE, Diamond GM, Siqueland L, Isaacs L. Attachment-based family therapy for depressed adolescents: a treatment development study. J Am Acad Child Adolesc Psychiatry 2002;41:1190–1196. 140. Sandler IN, West SG, Baca L et al. Linking empirically based theory and evaluation: the family bereavement program. Am J Community Psychol 1992;20:491–521. 141. Barbato A, DÕAvanzo B. Marital therapy for depression. Cochrane Database Syst Rev 2006;2:CD004188. 142. Malhi GS, Parker GB, Crawford J, Wilhelm K, Mitchell PB. Treatment-resistant depression: resistant to definition? Acta Psychiatr Scand 2005;112:302–309. 143. Burrows GD, Norman TR, Judd FK. Definition and differential diagnosis of treatment-resistant depression. Int Clin Psychopharmacol 1994;9(suppl. 2):5–10. 144. Thase ME, Greenhouse JB, Frank E et al. Treatment of major depression with psychotherapy or psychotherapypharmacotherapy combinations. Arch Gen Psychiatry 1997;54:1009–1015. 145. Berlim MT, Turecki G. What is the meaning of treatment resistant ⁄ refractory major depression (TRD)? A systematic review of current randomized trials. Eur Neuropsychopharmacol 2007;17:696–707. 146. Szegedi A, Muller MJ, Anghelescu I, Klawe C, Kohnen R, Benkert O. Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression. J Clin Psychiatry 2003;64:413–420. 147. Nierenberg AA, Farabaugh AH, Alpert JE et al. Timing of onset of antidepressant response with fluoxetine treatment. Am J Psychiatry 2000;157:1423–1428. 148. Trivedi MH, Morris DW, Grannemann BD, Mahadi S. Symptom clusters as predictors of late response to antidepressant treatment. J Clin Psychiatry 2005;66:1064– 1070. 149. Sackeim HA, Roose SP, Lavori PW. Determining the duration of antidepressant treatment: application of signal detection methodology and the need for duration adaptive designs (DAD). Biol Psychiatry 2006;59:483–492. 150. Burke WJ, Gergel I, Bose A. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry 2002;63:331–336. 151. Rudolph RL, Derivan AT. The safety and tolerability of venlafaxine hydrochloride: analysis of the clinical trials

Depression CPR

152.

153.

154.

155.

156.

157.

158.

159.

160.

161.

162.

163.

164.

165.

166.

167.

168.

database. J Clin Psychopharmacol 1996;3(suppl. 2):54S– 59S; discussion 9S-61S. Adli M, Baethge C, Heinz A, Langlitz N, Bauer M. Is dose escalation of antidepressants a rational strategy after a medium-dose treatment has failed? A systematic review. Eur Arch Psychiatry Clin Neurosci 2005;255:387–400. Bschor T, Bauer M. Efficacy and mechanisms of action of lithium augmentation in refractory major depression. Curr Pharm Des 2006;12:2985–2992. Bauer M, Forsthoff A, Baethge C et al. Lithium augmentation therapy in refractory depression-update 2002. Eur Arch Psychiatry Clin Neurosci 2003;253:132–139. Papakostas GI, Shelton RC, Smith J, Fava M. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a metaanalysis. J Clin Psychiatry 2007;68:826–831. Furukawa T, McGuire H, Barbui C. Low dosage tricyclic antidepressants for depression. Cochrane Database Syst Rev 2003;3:CD003197. Joffe RT, Singer W, Levitt AJ, MacDonald C. A placebocontrolled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression. Arch Gen Psychiatry 1993;50:387– 393. Joffe RT, Marriott M. Thyroid hormone levels and recurrence of major depression. Am J Psychiatry 2000; 157:1689–1691. Ng F, Dodd S, Berk M. Combination pharmacotherapy in unipolar depression. Expert Rev Neurother 2006;6:1049– 1060. Dodd S, Horgan D, Malhi GS, Berk M. To combine or not to combine? A literature review of antidepressant combination therapy. J Affect Disord 2005;89:1–11. Malhi GS, Ng F, Berk M. Dual-dual action? Combining venlafaxine and mirtazapine in the treatment of depression. Aust NZ J Psychiatry 2008;42:346–349. Licht RW, Qvitzau S. Treatment strategies in patients with major depression not responding to first-line sertraline treatment. A randomised study of extended duration of treatment, dose increase or mianserin augmentation. Psychopharmacology 2002;161:143–151. Ruhe HG, Huyser J, Swinkels JA, Schene AH. Dose escalation for insufficient response to standard-dose selective serotonin reuptake inhibitors in major depressive disorder: systematic review. Br J Psychiatry 2006;189:309–316. Ruhe HG, Huyser J, Swinkels JA, Schene AH. Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry 2006;67:1836–1855. Peselow ED, Filippi AM, Goodnick P, Barouche F, Fieve RR. The short- and long-term efficacy of paroxetine HCl: B. Data from a double-blind crossover study and from a year-long term trial vs. imipramine and placebo. Psychopharmacol Bull 1989;25:272–276. Birmaher B, Brent D, Issues AWGoQ et al. Practice parameter for the assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child Adolesc Psychiatry 2007;46:1503–1526. National Institute for Health and Clinical Excellence. Depression in children and young people: clinical guideline 28. London: NHS, 2005. Thorpe L, Whitney DK, Kutcher SP, Kennedy SH, Group CDW. Clinical guidelines for the treatment of depressive disorders. VI. Special populations. Can J Psychiatr – Rev Can Psychiatr 2001;46(suppl. 1):63S–76S.

169. Wilson KC, Mottram PG, Vassilas CA. Psychotherapeutic treatments for older depressed people. Cochrane Database Syst Rev 2008;1:CD004853. 170. National Institute for Health and Clinical Excellence. Antenatal and postnatal mental health: clinical Guideline 45. London: NHS, 2007. 171. ACOG Committee on Practice Bulletins–Obstetrics. ACOG Practice Bulletin: clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol 2008;111:1001– 1020. 172. Therapeutic Goods Administration. Prescribing medicines in pregnancy: medicines classified since 1999 publication, 2007 [cited 30 May 2008]. Available at: http://www.tga.gov.au/docs/html/medpreg.htm. 173. Pollack MH. Comorbid anxiety and depression. J Clin Psychiatry 2005;8:22–29. 174. Davis L, Uezato A, Newell JM, Frazier E. Major depression and comorbid substance use disorders. Curr Opin Psychiatry 2008;21:14–18. 175. Tiet QQ, Mausbach B. Treatments for patients with dual diagnosis: a review. Alcohol Clin Exp Res 2007;31:513– 536. 176. Newton-Howes G, Tyrer P, Johnson T. Personality disorder and the outcome of depression: meta-analysis of published studies. Br J Psychiatry, 2006;188:13–20. 177. Whitehead C, Moss S, Cardno A, Lewis G. Antidepressants for people with both schizophrenia and depression. Cochrane Database Syst Rev 2002;2:CD002305. 178. Evans DL, Charney DS, Lewis L et al. Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry 2005;58:175–189. 179. Benton T, Staab J, Evans DL. Medical co-morbidity in depressive disorders. Ann Clin Psychiatry 2007;19:289– 303. 180. Linde K, Mulrow CD, Berner M, Egger M. St JohnÕs wort for depression. Cochrane Database Syst Rev 2005;2:CD000448. 181. Ivanovski B, Malhi GS. The psychological and neurophysiological concomitants of mindfulness forms of meditation. Acta Neuropsychiatr 2007;19:76–91. 182. Mead GE, Morley W, Campbell P, Greig CA, McMurdo M, Lawlor DA. Exercise for depression. Cochrane Database Syst Rev 2008;4:CD004366. 183. Dolder CR, Nelson M, Snider M. Agomelatine treatment of major depressive disorder. Ann Pharmacother 2008;42:1822–1831. 184. Gross M, Nakamura L, Pascual-Leone A, Fregni F. Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies. Acta Psychiatr Scand 2007;116:165– 173. 185. Malhi G, Sachdev P. Novel physical treatments for the management of neuropsychiatric disorders. J Psychosom Res 2002;53:709–719. 186. Fitzgerald PB, Daskalakis ZJ. The use of repetitive transcranial magnetic stimulation and vagal nerve stimulation in the treatment of depression. Curr Opin Psychiatry 2008;21:25–29. 187. Malhi G, Loo C, Cahill C, Lagopoulos J, Mitchell P, Sachdev P. ‘‘Getting physical’’: the management of neuropsychiatric disorders using novel physical treatments. Neuropsychiatr Dis Treat 2006;2:165–179.

25

Malhi et al. 188. Tuunainen A, Kripke DF, Endo T. Light therapy for nonseasonal depression. Cochrane Database Syst Rev 2004; 2:CD004050. 189. Even C, Schroder CM, Friedman S, Rouillon F. Efficacy of light therapy in nonseasonal depression: a systematic review. J Affect Disord 2008;108:11–23. 190. Winkler D, Pjrek E, Iwaki R, Kasper S. Treatment of seasonal affective disorder. Expert Rev Neurother 2006;6:1039–1048. 191. Kennedy SH, Lam RW, Cohen NL, Ravindran AV, Group CDW. Clinical guidelines for the treatment of depressive disorders. IV. Medications and other biological treatments. Can J Psychiatr – Rev Can Psychiatr 2001;46:38S– 58S.

26

192. MIMS. MIMS: Issue 1 2008 (Feb ⁄ Mar). February ⁄ March 2008 ed. Sydney: CMP Medica, 2008. 193. Facts & Comparisions (2008) Drug facts and comparisons, pocket version 2009, Lippincott Williams & Wilkins. 194. Peretti S, Judge R, Hindmarch I. Safety and tolerability considerations: tricyclic antidepressants vs. selective serotonin reuptake inhibitors. Acta Psychiatr Scand Suppl 2000;403:17–25. 195. Krishnan KR. Revisiting monoamine oxidase inhibitors. J Clin Psychiatry 2007;68(suppl. 8):35–41. 196. O’Conner N, Warby M, Raphael B, Vassallo T. Changeability, Confidence, Common Sense, Corroboration and Comprehensive suicide Risk Assessment. Australian Psychiatry 2004;12:352–360.