Original Papers
DOI: 10.5455/bcp.20140107040932
Assessment of Psychopharmacological Treatment in Adolescents with Obsessive Compulsive Disorder Sevcan Karakoc1, Osman Abali2
ÖZET:
ABSTRACT:
Obsesif kompulsif bozukluğu olan ergenlerde psikofarmakolojik tedavinin değerlendirilmesi
Assessment of psychopharmacological treatment in adolescents with obsessive compulsive disorder
Amaç: Obsesif kompulsif bozukluk (OKB) tanısı alan erişkinlerin 1/3-1/2’sinde hastalığın çocuk ve ergenlikte başladığı saptanmıştır. Erken başlangıçlı OKB tedavisi erişkinlere göre daha zordur, ayrıca bu konuda psikofarmakolojik çalışmalar kısıtlıdır. Ayrıca ergen ve çocuk OKB kliniği ve tedavisi birbirinden farklıdır. Bu araştırmada çocuk psikiyatrisi polikliniğinde takip edilmekte olan OKB tanılı ergenlerin farmakolojik tedavisi değerlendirilmiştir. Yöntem: İstanbul Tıp Fakültesi Çocuk Psikiyatrisi polikliniğine başvurmuş ve DSM-IV TR’e göre OKB tanısı ile 2 yıldır takip edilen 12-18 yaşları arasındaki 30 hastanın (12 erkek,18 kız hasta) dosyası geriye dönük olarak taranmıştır. OKB özellikleri, OKB alt tipleri, eşlik eden diğer tanılar, kullanılan birinci ilaç seçenekleri, en son almakta olduğu ilaç ve dozu, eğer varsa herhangi bir zamanda aldığı güçlendirme tedavisi, yan etkiler, OKB açısından aile öyküsü ve hastaların klinik gidişatı değerlendirilmiştir. Bulgular: Çalışmada hastaların en son almakta olduğu ilaç grubu, 1 hastada trisiklik antidepresan (klomipramin) ve 1 hastada seçici noradrenalin geri alım inhibitörü (venlafaksin) iken, çalışma grubunun %93’ünde (n=28) seçici serotonin geri alım inhibitörüdür (SSGİ). Bunların %39,3’ünü (n=11) sertralin, %25’ini (n=7) fluoksetin, %3,6’sını (n=1) paroksetin kullananlar oluştururken; essitalopram, sitalopram ve fluvoksamin alanlar ayrı ayrı herbiri %10,7’yi (n=3) oluşturmaktaydı. Olguların %43’ünde (n=13) antipsikotiklerle güçlendirme tedavisinden yararlanılmıştır. Oniki olguda ilk seçenek risperidon, 1 olguda ise olanzapin kullanılmıştır. İlk başta risperidon kullanan 12 hastanın 3’ünde yetersiz yanıt ve hiperprolaktinemi olduğu için ketiyapine geçilmiş, bunlardan birisinde kilo artışı fazla olduğu için daha sonra ziprasidon kullanılmıştır. Güçlendirme tedavisinde kullanılan diğer ilaçlar 2 olguda benzodiazepin (alprazolam), 1 olguda antiepileptik grubudur (karbamazepin). Kombinasyon tedavisi olarak klomipramin ve fluvoksamin 4 olguda kullanılmıştır. En sık eşlik eden tanı yaygın anksiyete bozukluğudur. Eşlik eden anksiyete şiddeti arttıkça tedaviye yanıtsızlık artmaktadır. Sonuç: Ergen OKB tedavisi zordur. Çoklu ilaç kullanımı dirençli olguların tedavisinde sıklıkla kullanılmaktadır.
Objective: Among adult patients with obsessivecompulsive disorder (OCD), 1/2 -1/3 of them have had OCD symptoms since their childhood. The management of OCD in children is more difficult than in adults. However the data on psychopharmacology is inadequate and mainly based on adult cases. We aimed to review the pharmacotherapy of the adolescent patients who were followed with a diagnosis of OCD. Method: Thirty adolescent (12 male, 18 female) OCD patients, aging between 12-18 years who have been followed in Istanbul Medical Faculty Child Psychiatry outpatient clinic for 2 years were included. The diagnosis was made according to criteria of DSM-IV TR. Presenting symptoms, subtypes, comorbid psychiatric diseases, primary medications, augmentation treatments, adverse effects, family history for OCD and clinical improvement were assessed retrospectively. Results: As a final medication, 93.3% (n=28) of the group received selective serotonine reuptake inhibitors (SSRI), 1 case was on venlafaxine, another patient was on clomipramine treatment. Among SSRI group, percentages of drug choices is as follows: 39.3% (n=11) for sertraline, 25% (n=7) for fluoxetine, 10,7% (n=3) for escitalopram, 10,7% (n=3) for citalopram, 10,7% (n=3) for fluvoxamine and 3.6% (n=1) for paroxetine. Antipsychotic agents (mostly risperidone) are used for augmentation in 13 cases (43%). The other agents for augmentation are benzodiazepines (alprazolam) (n=2), and antiepileptic (carbamazepine) (n=1). As a combination treatment to SSRI, 4 patients also recieved fluvoxamine and clomipramine. The most common comorbid disorder in the group was generalized anxiety disorder. When comorbid conditions’ severity increased, the response rate decreased. Conclusion: Treatment of OCD in adolescence is diffucult. Polypharmacotherapy is mostly used in case of treatment resistance.
1 M.D., Bakirkoy Mental Health Training and Research Hospital, Child and Adolescent Psychiatry Department, Istanbul - Turkey 2 Assoc. Prof. Dr., Istanbul University, Istanbul Medical Faculty, Department of Child and Adolescent Psychiatry, Istanbul - Turkey
Address reprint requests to: Assoc. Prof. Dr. Osman Abali, Istanbul University, Istanbul Medical Faculty, Department of Child and Adolescent Psychiatry, Suleymaniye, Istanbul - Turkey Phone: +90-212-440-0000/12818 E-mail address:
[email protected]
Keywords: adolescent, obsessive compulsive disorder treatment, augmentation
Date of submission: November 12, 2013
Bulletin of Clinical Psychopharmacology 2014;24(1):XXX
Date of acceptance: January 7, 2014
Anahtar sözcükler: ergen, obsesif kompulsif bozukluk tedavisi, güçlendirme tedavisi Klinik Psikofarmakoloji Bulteni 2014;24(1):XXX
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Declaration of interest: S.K., O.A.: The authors reported no conflict of interest related to this article.
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Assessment of psychopharmacological treatment in adolescents with obsessive compulsive disorder
INTRODUCTION Obsessive-compulsive disorder (OCD) is a relatively common, chronic neuropsychological disorder. It is defined by persistent and unwanted thoughts/images called obsessions and ritualistic behaviors or mental acts called compulsions. It used to be classified as an anxiety disorder in DSMIV-TR (1), but in the newly published DSM-V, OCD is under a different chapter as obsessive compulsive and related disorders (2). It is seen in almost 1% to 2% of the population (3). In Turkey, the prevalance was 2.7% in clinically referred population in a study published in 2002 (4). Individuals with OCD suffer from functional impairment and they have poor quality of life. It is known that 1/2 -1/3 of adult patients having OCD have experienced their diseases since childhood (5). It is suggested that OCD has a bimodal distribution, peaks in preadolescent childhood and young adulthood have different disease characteristics. In childhood type, OCD is seen in a 3:2 boys:girls ratio whereas it is equal in adult ages (6). Obsessions and compulsions tend to change during the lifetime. Symptoms experienced in childhood may be different from those present in adulthood. Adults with OCD recognize that their obsessions and compulsions are excessive or unreasonable. However this requirement for diagnosis is not needed for children. Children may lack adequate cognitive awareness to make this judgement. Most children go through developmental stages especially in preschool period (2-6 years) characterized by compulsive behaviors and rituals (E.g bedtime, mealtime rituals) that are normal. So, it is challenging to differentiate normal and abnormal behaviors in children (7). The prevalence of underdiagnosed OCD cases are high, therefore clinicians have to investigate OCD symptoms in routine practice. Early onset and late onset childhood OCD are quite different from each other in terms of phenotype, comorbid conditions and treatment (6). Fears of contamination, catastrophic thoughts of parental loss and symmetry are the most common obsessions and cleaning, checking and 2
arranging are the most common compulsions. Early onset OCD cases show multiple symptoms and compulsions with sensory pheneomena (8). Attention deficit hyperactivity disorder (ADHD) and tic disorders are seen in younger ages and mood and psychotic diasorders are associated with postpubertal ages (7). Watson et.al performed a metaanalysis of 161 young patients and they reported cognitivebehavioral therapy (CBT) as a first step in management of OCD (9). Cognitive behavioral psychotherapy is indicated in mild to moderate forms of OCD according to American Academy of Child and Adolescent Psychiatry (AACAP) guidelines (7). March et. al suggests 12 weeks of CBT protocol with phases of psychoeducation, cognitive training, mapping the symptoms and disease, exposure and response prevention and finally relapse prevention (10). Medication is indicated in moderate to severe cases in addition to CBT. Even in mild cases, pharmacotherapy can be given in early stages due to many factors: depending on the child (if he/she is less motivated to therapy), family (if chaotic), disease (if with a poor insight) and clinician (if he/she is a less skilled practitioner). Also presence of comorbid conditions may impair the success of CBT (7). Selective serotonin receptor inhibitors (SSRI) are the first line drugs for OCD. Fluoxetine, sertraline and fluvoxamine are approved by the United States Food and Drug Administration (FDA) as medication for OCD, the other SSRI classes are also effective in treatment of OCD (7,11). Although clomipramine is the most effective approved agent, it is not a drug of first choice due to its severe side effects (7,12). Combined therapy (drug and CBT together) is the most recommended treatment for OCD (10). Recommended typical dose range of drugs are as follows: For clomipramine 50-200 mg/day, fluoxetine 10-80 mg/day, sertraline 50-200 mg/day, fluvoxamine 50-300 mg/day, paroxetine 10-60 mg/day, citalopram 10-60 mg/day in children and adolescents (7). Treatment resistance is the term used when satisfactory responses are not achieved after
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Karakoc S, Abali O
standard adequate therapy for OCD, which are trials of two different maximum suggested or tolerated dose of SSRI or one SSRI and clomipramine usage for minimum duration of 10 weeks with stable dose for 3 weeks (7,13). Response is determined by reduction of at least 25% of baseline symptoms (observed clinically or rated on scales). Many augmentation strategies are suggested by experts. Adjunctive medications are frequently used in adult practice successfully (14). Risperidone, olanzapine, aripiprazole are found to be effective in more than 50% of cases in augmentation treatment (13). However, limited data on augmentation in OCD children and adolescents is present. Case series using risperidone, aripiprazole supply empiric evidence in literature (13,15). Adult studies showed effectiveness of neuroleptic augmentation. For example, Savaş et al. investigated effectiveness of ziprasidone and quetiapine as adjunct therapy in refractory OCD and made a comparasion. They reported that both treatment modalities were effective, but clinical improvement in quetiapine group (80%) was superior to ziprasidone group (44.4%) (16). Since the negative consequences of OCD are harmful for school and social environment, family life and personal wellbeing of the youth; several augmentation strategies have been developed against the failure in treatment of OCD. On the other hand evidence of pharmacotherapy in early onset OCD is lacking (17,18). In this study, we aimed to evaluate the pharmacological treatment (primary and
augmentation medications) of OCD in clinically referred adolescent individuals, and to provide effective examples of augmentation medications in refractory cases. Other purpose of this study was to assess presenting symptoms, OCD subtypes, comorbid psychiatric diseases, adverse effects of medication, family history for OCD and clinical improvement retrospectively.
METHOD Adolescent patients with a diagnosis of OCD, aging between 12-18 years who have been followed in the Istanbul Medical Faculty Child Psychiatry outpatient clinic for a 2-year period were included. The diagnosis of OCD was made according to DSM-IV-TR classification (1). The charts of the patients were reviewed retrospectively and the individuals who gave informed consents were gathered for data collection. In order to get a homogenous sample, subjects were selected based on these criteria: subjects with similar socioeconomic status (middle class), having both parents alive and living together, having a history of pharmacotherapy for OCD and not having a chronic physical disorder. None in the study group were mentally or developmentally handicapped. Presenting symptoms, subtypes, c o m o r b i d p s y c h i a t r i c d i s e a s e s, p r i m a r y medications, augmentation treatments, adverse effects, family history for OCD and clinical improvement were assessed. Descriptive statistics (frequency, proportion, mean, standard deviation, minimum, maximum) were used for data analysis.
Table 1: Descriptive features of parents Age (mean, min-max) in
Mothers 40.4 (31-56)
Fathers 44.5 (35-60)
Years Education n % n % No school 1 3 1 3 Primary school degree 20 67 17 57 High school degree 6 20 6 20 University degree 3 10 6 20 Profession status Nothaving –housewife for 25 83 5 17 mothers/ retired for fathers Having a job 5 17 25 83
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Assessment of psychopharmacological treatment in adolescents with obsessive compulsive disorder
RESULTS The study group was composed of 30 adolescent OCD patients. Twelve of them (40%) were boys, 18 of them (60%) were girls. The mean age of the sample was 14.0±1.8. Sixteen cases were the eldest child, 13 of them were the youngest child and only 1 of them was the middle child in their families. Their parents’ sociodemographic data is shown on Table 1. Family history for any mental disorder was positive in 53% of the cases. Twenty percent of the cases (n=6) had mothers and/or fathers with diagnosis of OCD. Mean referral age with OCD symptoms was 12.8 (range 10 to 17 years old). Only 7 subjects (23%) reported that they had only one type of clinical presentation which was contamination-cleaning. The others experienced more than one type of OCD symptoms. Clinical presentation of OCD in our sample is shown in Table 2. Seventy percent of the adolescents suffered from a comorbid disorder. Anxiety disorders were the most common comorbid condition with a ratio of 37% totally 11 cases. Generalized anxiety disorder (n=6), seperation anxiety disorder (n=2) and social anxiety disorder (n=3) were comorbid with OCD. One case was diagnosed as having both tic disorder and depressive disorder in addition to OCD. All individuals with a diagnosis of comorbid Table 2: Clinical presentation of OCD Subtypes of OCD
n
%
Contamination-washing-cleaning Religious-aggresive thoughts-rituels Sexual thoughts Ordering-checking
18 60 9 30 5 17 8 27
Presence of Comorbid disorders* None Any anxiety disorder Generalized anxiety disorder Seperation anxiety Social anxiety disorder ADHD Depression Tic disorders
9 30 11 37 6 20 2 6 3 9 5 17 4 13 2 6
*one case had two comorbid conditions (tic disorder and depression) additional to OCD
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attention deficit hyperactivity disorder were also medicated psychostimulant treatment. Every case received psychoeducation and nonstructured supportive therapy. After diagnostic interview, clinicans educated families about OCD and they emphasized on parents’ disengagement from their child’s OCD behaviors in order to avoid family accomodation. Patients and their parents were informed about nature of the disease, vicious cycle of the disease. They learned how to monitor their symptoms and adverse effects of the prescribed drugs. Every clinic visit, side effects, percentage of symptom reduction and family participation in OCD rituals were evaluated. Due to limited time in outpatient clinic conditions and lack of experienced CBT therapists, pharmacotherapy was the primary choice for these subjects. The initial management step was administration of a drug from SSRI class in most of the patients. The tricyclic antidepressant drug clomipramine was chosen for 2 subjects at the first step. Table 3 summarizes the first drug choices in our group. A l t h o u g h m a x i mu m r e c o m m e n d e d o r maximum tolerated dose and duration (at least 10 weeks) had been supplied, the expected response was not achieved after first drug management in 5 cases. Nonresponders were determined as patients with ≤25% reduction in symptoms. Response was assessed by clinical interview and symptom severity depending on patients’ and parents’ reports filled on the chart of the patient. When a treatment failure was encountered, a second SSRI trial was given. Fluoxetine was given to 2 individuals who were unresponsive to escitalopram. Fluoxetine was changed in 3 subjects
Table 3: Initial step of medication in management of OCD Medication
Number of cases
n (%)
Sertraline Fluoxetine Citalopram Escitalopram Fluvoxamine Clomipramine
10 (33.3) 10 (33.3) 3 (10.0) 3 (10.0) 2 (6.7) 2 (6.7)
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Table 4: Serotonin Reuptake Inhibitors used on the final step before augmentation/ Medication
n
%
mg/day (max.dose)
Sertralin Fluoxetine Citalopram Escitalopram Fluvoxamine Paroxetine Venlafaxine Clomipramine
11 36.7 7 23.3 3 10.0 3 10.0 3 10.0 1 3.3 1 3.3 1 3.3
150 40 50 30 100 40 225 50
Table 5: Medications used in augmentation step (20 trials in 16 treatment resistant cases) Drug
Max. Dose (mg/day)
Subjects (n)
Risperidone 2 12 Quetiapine 100 3 Ziprasidone 40 1 Olanzapine 2.5 1 Carbamazepine 400 1 Alprazolam 1 2
to SNRI venlafaxine (n=1), sertraline (n=1) and escitalopram (n=1). As a side effect experienced with SSRI, insomnia was reported in 4 cases. Mirtazapine (n=2), alprazolam (n=1) and trazodone (n=1) were prescribed in order to get rid of this sleep problem. Four cases received a combination of antidepressants. These adjunctive combinations were “clomipramine+fluoxetine”, “clomipramine+ fluvoxamine”, “mirtazapine+ fluoxetine” and “mirtazapine+paroxetine”. Mirtazapine was prefferred for sleep problems and used as adjunct therapy. Augmentation strategy was considered in 53.3% (n=16 ) of the group (Table 5). They were called refractory cases which mean they showed no or little response to adequate therapy, which are trials of two different maximum suggested or tolerated dose of SSRI or one SSRI and clomipramine usage for OCD for minimum duration of 10 weeks with stable dose for 3 weeks. Response is determine by reduction of at least 25% of baseline symptoms observed clinically or reported by the children and their parents. Among these cases, 4 of them also had second augmentation medication. Antipsychotic adding strategy was the most
commonly used augmentation which was preferred for 13 subjects (43% of the whole sample, 81% of the treatment resistant group). Atypical antipsychotics risperidone (n=12 subjects) and olanzapine (n=1) were given with parents’ permission. Due to hyperprolactinemia, moderate sedation and lack of response; quetiapine was prescribed to individuals (n=3) who were on risperidone treatment. One of these 3 cases on quetiapine treatment had experienced excessive weight gain (7 kg in 4 months), therefore ziprasidone was tried as a third choice for augmentation after risperidone and quetiapine. Medications other than antipsychotics used for augmentation in this study were benzodiazepine (alprazolam) in 2 subjects and an antiepileptic (carbamazepine) in 1 subject with resistant OCD. The clinical outcome was evaluated from the patients’ charts. Unfortunately, we didnot finde any data about prognosis in 4 cases. Symptom reduction among remaining 26 subjects was 25% to 90% with a mean of 63%. Clinical improvement was measured by observation and self report. As a dipnote stated in the patients’ files; when severity of comorbid anxiety and tic disorder increased, treatment of OCD became more complicated.
DISCUSSION We aimed to evaluate the clinical characteristics and pharmacological treatment of adolesecent individuals with OCD in a clinically referred sample retrospectively. We grouped OCD symptoms and 77% of cases suffered from mixed type obsessions/compulsions. The pure form of OCD symptom - contamination and cleaning accounted for 23% of the cases. We found that contamination obsession and cleaningwashing compulsion was the most common (60%). Religious-aggressive, ordering-checking, and sexual thoughts were reported in 30%, 27% and 17% respectively. Our data is consistent with previous findings. Diler and Avcı reported that the most prevalent obsession was contamination (49%) and the most common compulsion was washing/cleaning (68%). The second leading
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Assessment of psychopharmacological treatment in adolescents with obsessive compulsive disorder
compulsion was controlling and the third one was obsessional thoughts about sexuality and/or aggression in their study (4). Bloch et al. made a metaanalysis of symptom structure in OCD in 2008. They grouped OCD symptoms according to 4 factors: 1) Symmetry, repeating, ordering; 2) forbidden thoughts (religious, sexual, agressive ); 3) cleaning and contamination, somatic and 4) hoarding. They reviewed 21 studies with 5,124 subjects and only 4 studies had child participants (n=679). Symptoms in children were found to be the highest in factor 1 (28.7%) and factor 2 was the second highest (19.9%) whereas factor 4 was seen in 16.7% and factor 2 in 16.4% (14). In our study comorbid psychiatric disorders were prevalent (70%) the same as in the study conducted by Swedo et al. They found a high comorbidity rate as 74%. Tic disorder (30%), major depression (26%), learning disorders (24%), ADHD (10%), generalized anxiety disorder (16%) were reported in that study. (19). Comorbidity rate for any anxiety disorder was 37%, ADHD was 17%, depressive disorders was 6% and tic disorders was 6% in our sample. The tic disorder rate in our research is smaller than in the study conducted by Swedo et al.. This may have resulted from the selection of sample and differences of populations in two studies. Also adolescents and their families might be more worried by tics than obsessions. Tourette syndrome is seen in 5% of OCD patients. Other anxiety disorders are seen in more than half of the patients and also disruptive behaviors are reported as a comorbid situation in 22% of OCD cases. Tics and mood disorders are known to complicate OCD symptoms (12). In our study SSRI was the first line treatment in 94% of all cases. Clomipramine was precribed for only 2 cases. Although clomipramine is known as standard treatment, severe side effects (especially cardiac abnormalities) are observed and close monitoring is needed. Therefore SSRI drugs quickly replaced clomipramine (20). Sertraline and fluoxetine, citalopram, escitalopram and fluvoxamine were preferred medications in our sample. Current FDA approval for pediatric OCD involves 3 SSRI agents; fluoxetine, sertraline and 6
fluvoxamine. Citalopram (21) and paroxetine are also found effective in children but randomized controlled trials on children are limited (20). This information might affect the clinician’s attitude towards drug choice in our clinic. Geller et al. completed a metaanalysis of pharmacotherapy in pediatric OCD, they researched 12 studies with a total of 1,044 participants. They showed that serotonergic drugs are highly significantly superior to placebo and no statistical difference is observed among SSRI groups. The overall effect is similar, so side effect profile, the individual’s liver condition, and the half life of the drug must be considered before chosing a SSRI (22). Adverse effects of SSRI other than sleep problems were not observed in our study.This may be because SSRIs are known to be well tolerated or data on side effects might be not be fully detailed in patients’ files. So that it may be a result of the methodology of this study. But 4 cases reported insomina and additonal drugs were administered. Safer and Zito investigated the treatment of emerged side effects of SSRI in young cases. Their study showed that activation and nausea are more c o m m o n i n c h i l d r e n t h a n a d o l e s c e n t s. Somnolence is seen 11.3% of cases whereas the insomnia rate is 12% (23). Since 40% to 60% of patients do not respond well to serotonergic agents, new strategies must be developed for treating resistant/ complicated cases (20). If one SSRI is ineffective then a second SSRI should be trialed (high doses may be needed to effectively treat OCD). If the second SSRI fails too, an atypical antipsychotic combination with SSRI is supported in recent researches (21). Taking into consideration the fact that treatment of OCD is complicated, the studies of antipsychotics with both serotonergic and dopaminergic effects are promising. Several potentiation strategies including off-label usage of antipsychotics (mostly risperidone, quetiapine) have been studied. In some cases, an antiobsessive effect is obtained in low doses, while high doses may cause exacerbations of the obsessive compulsive symptoms. In our study, treatment resistant OCD cases were 53% of all individuals. The
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nonresponders and/ or partial responders rate was high in our study. This may be derived from the characteristics of the cases since comorbidity was common in our group. Psychiatric comorbidity may have a significant influence on treatment response. In addition to SSRI drugs, clomipramine, neuroleptics, clonazepam are used in augmentation medications (7). It is suggested that dopamine and serotonin systems supply a balance with each other and many other systems, such as glutamate, neuropeptides, and gonadal steroids may be involved in the biochemistry of OCD (25). In this study antipsychotic augmentation strategy was the most commonly preffered way for 13 subjects which means 43% of the whole sample and 81% of the treatment resistant group. Medication other than antipsychotics used for augmentation in this study were benzodiazepine (alprazolam) in 2 subjects and an antiepileptic (carbamazepine) in 1 subject with resistant OCD. Clonazepam with its unique serotonergic effect among benzodiazepines has been used in OCD, but data about alprazolam is highly limited. Bahali et. al reported a young case with schizophrenia and OCD. They prescribed paroxetine, alprazolam and quetiapine, after they added risperidone, they observed improvement in OCD symptoms (26). Some anticonvulsants (mainly topiramate, gabapentin) are used as monotherapy or augmentation in OCD, since OCD is a type of anxiety disorder (27). Literature suggests carbamazepine use in OCD with comorbid epilepsy or treatment resistant OCD depending on some adult case series. Aggarwal and his colleagues reported a case diagnosed as OCD with EEG abnormality who was successfully treated with carbamazepine (28). Our case was nonepileptic; but she was first case report, she benefitted from carbamazepine added to fluvoxamine, quetiapine combination. For neuroleptic augmentation; risperidone was delivered in 12 cases, quetiapine in 3 cases, olanzapine in 1 and ziprasidone in 1 case. Haloperidol and risperidone are known as effective in the treatment of OCD and comorbid tics. Atypical antipsychotics are investigated in
case reports and trials, no controlled studies exist in youth. Risperidone is the most commonly used drug in augmentation in OCD due to its risk benefit rate (29). It blocks dopamine-2 receptors, as well as 5HT-2A and 5HT-6, alpha-1 and 2 adrenergic receptors, so it causes a variety of changes in anxiety, cognition, mood and behavior (25). Due to sedation and hyperprolactinemia, we added quetiapine instead of risperidone in 3 subjects. Unfortunately one of our cases put on much weight so we eliminated quetiapine and added ziprasidone. Masi et. al reported that sedation and weight gain are the most common adverse effects of risperidone in their study population (13). Results of quetiapine are c o n t r a d i c t o r y, s o m e r e s e a r c h e r s f o u n d effectiveness, some showed nonresponsiveness (30). Savaş et al. reported that quetiapine is more effective than ziprasidone in refractory cases. They observed good tolerance to both medications, but they reported weight gain in 3 cases due to an adverse effect of quetiapine (16). Previous studies (case reports and open studies) support ziprasidone in OCD with comorbid conditions. Yeghiyan and his colleaques administered ziprasidone to adolescents (n=14) with OCD plus Tourette syndrome and they observed much improvement in OCD symptoms with high doses (>80 mg/day) of ziprasidone (31). In fact, our case, a female 14 years old diagnosed as OCD plus ADHD, benefitted from 40 mg of ziprasidone augmentation. A comparasion study was conducted by Maina et al.; they found no significant difference between risperidone and olanzapine augmentation in OCD (32). Comparasion study in adult individuals done by Savas et al. showed that there is a significant difference between effectiveness of quetiapine and ziprasidone during course of the treatment, they reported that both medications were effective in symptom reduction but quetiapine was superior. (16). Improvement in symptoms was seen in 25-90% of our population with a mean of 63% response to all groups of medications. The rate of improvement is found to be similar in the study conducted by
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Assessment of psychopharmacological treatment in adolescents with obsessive compulsive disorder
Masi and his colleagues They reported a 58.1% response rate in antipsychotic augmentation in OCD (33). Our study has methodological limitations. This study is a medical chart review with a relatively small sample. Therefore clinical symptom severity and improvement was assessed on clinicans’ examination, no specific measures were used. Our clinic is a third-level reference center, so we can not generalize the results of our data due to this selection bias since these patients may be more complicated cases. Effects on unresponsiveness to conventional treatment by factors such as gender or OCD subtypes were not evaluated. Our study has some strenghts. Our study is relatively large treatment refractory OCD group comparing to case studies present in the literature. The findings of this study is unique in Turkey for
early pharmacological intervention trials for OCD. This study shares important clinical experiences on pharmacotherapy of children onset OCD and reports effective coping strategies with resistant cases. Our study contributes to literature which has limited data for augmentation in OCD children and adolescents. In summary, this study shows that comorbidity is high in adolescent OCD and treatment resistance is a common problem in this group. The first step in medication is the use of SSRI agents, antipsychotics are found to be effective when augmentation is planned. Our study is unique in our country in providing such significant pharmacotherapy experience. Randomized, controlled studies, as well as larger samples are needed in order to evaluate efficacy and long term outcome of augmentation with neuroleptics.
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