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Adjunctive quetiapine may help depression comorbid with pervasive developmental disorders
Progress in Neuro-Psychopharmacology & Biological Psychiatry 33 (2009) 1570–1571
Contents lists available at ScienceDirect
Progress in Neuro-Psychopharmacology & Biological Psychiatry j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p n p
Letter to the Editor (Case report) Adjunctive quetiapine may help depression comorbid with pervasive developmental disorders
1. Introduction Depression is probably the most common psychopathology accompanying pervasive developmental disorders (PDD) however; relatively few reports have focused on its phenomenology and treatment (Ghaziuddin et al., 2002). Sertraline hydrochloride and quetiapine fumarate were used individually in this population for the treatment of self-injurious and repetitive behaviors, aggression, irritability, and transition induced anxiety and agitation (Chavez et al., 2007; Findling et al., 2004; Hellings et al., 1996; Martin et al., 1999; McDougle et al., 1998; Steingard et al., 1997). Quetiapine, though, is reported to have poor efficacy and/or tolerability and, reports of the use of either of these drugs to treat depression accompanying PDD are limited (Findling et al., 2004; Martin et al., 1999). Additionally, combined use of sertraline and quetiapine for depression in this population has not been reported up to now. Here; we report the successful treatment of major depressive disorder (MDD) and associated self-injurious behavior in an adolescent with Pervasive Developmental Disorder — Not Otherwise specified (PDD-NOS) and Moderate Mental Retardation (MR) with a combination of sertraline hydrochloride and quetiapine fumarate. 2. Case report A 17 year-old girl was brought to our department with complaints of “insomnia, tearfulness, irritability and, loss of appetite”. The complaints had been present for the past 6 months and she also started to display self-injurious behavior (i.e. head-banging). Daily functioning, verbal output and appetite were reduced. Sexualized behaviors, increased energy and verbal output or hyperactivity were not present, either before, or along with the complaints. The symptoms were not associated with menstruation or attributable to changes in routine. Information about stressors and/or abuse was absent. The patient was diagnosed with Autistic Disorder when she was 4 years old. The mother was diagnosed and successfully treated for an MDD with sertraline when the patient was 3 years old. She was still receiving sertraline 14 years later at the time of her daughter's consultation. Physical and neurological examinations and laboratory tests at the time of application were within normal limits. Wechsler Intelligence Scale for Children–Revised Edition (WISC-R) revealed a full-scale I.Q of 41 (Moderate MR) (Savasir and Sahin, 1995). At the initial evaluation the CGI-S score was judged to be 5 (“significantly impaired”) and an evaluation with Childhood Autism Rating Scale (CARS) demonstrated a score of 36 (mild–moderate autistic symptoms) (Guy, 1976; Schopler et al., 1980). She was diagnosed with Major Depressive Disorder, Single Episode and PDD-NOS according to DSM-IV-TR criteria and started on sertraline 25 mg/day (APA, 1994). Quetiapine 25 mg/day was added to control self-injurious behavior and for night-time sedation. At weekly 0278-5846/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2009.09.009
visits, sertraline was titrated to 50 mg/day and quetiapine 100 mg/day in divided doses, respectively. The presenting symptoms started to reduce at the first month of treatment and the patient returned to baseline functioning at the end of 3rd month; with the CGI-I subscale being much improved. No side effects were reported within the treatment period. Though the core symptoms (verbal and nonverbal communication, relating to people) did not change the last CARS evaluation at the 3rd month revealed a score of 33 with improvements in the “adjustment to change” and “fear or irritability” domains. Monthly visits up to the ninth month of treatment did not demonstrate any significant gains, therefore the drugs were discontinued. After discontinuation of drugs, telephone follow-ups at three month intervals were provided to the family and three years after the index episode, the patient remains free of depressive symptoms while continuing to receive supportive therapy which began at the 3rd month of treatment. 3. Discussion Here, we report the successful treatment of depression and associated self-injurious behavior in an adolescent female with PDDNOS and Moderate MR with sertraline hydrochloride and quetiapine fumarate. Sertraline was previously studied in patients with PDD in three open-label studies and in all of those studies, similar to our patient, sertraline was well tolerated with minimal side effects (Hellings et al., 1996; McDougle et al., 1998; Steingard et al., 1997). The findings that sertraline also helped increase adjustment to change along with depressive symptoms and that treatment gains were maintained in the three year follow-up of our patient are interesting and need to be replicated. Quetiapine was studied in two open-label studies on patients with PDD in dosages that ranged from 100 to 750 mg/day with about 25 to 33% of the patients being classified as treatment responders after treatments of 12 to 16 weeks (Findling et al., 2004; Martin et al., 1999). The fact that our patient did not experience any significant side effects while benefiting from treatment may be explained by differing dosing strategies, the diagnosis of PDD-NOS, drug naivety or gender. Much interest has been generated in using quetiapine in depression following reports of its use as an augmentative agent (Olver et al., 2008). Recently, quetiapine monotherapy at the doses of 150 mg and 300 mg/ day was found to be effective, safe and tolerable in the treatment of patients with MDD, with onset of symptom improvement demonstrated at the first week (Cutler et al., 2009). The mechanism of action of the quetiapine antidepressant response remains speculative and may be due to increased levels of dopamine or noradrenaline (Pira et al., 2004) in the brain or, alternatively it may be a non-specific effect of atypical antipsychotics (Thase et al., 2007). 4. Conclusion Considering all factors, our results suggest that quetiapine and sertraline may help depression accompanying PDD. However, this antidepressant effect can be due to quetiapine, sertraline or their
Letter to the Editor (Case report)
combination. In the light of recent studies which do not support the use of SSRIs in this population (King et al., 2009), our results should be deemed preliminary and be replicated with further studies.
References American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th Ed. American Psychiatric Association: Washington D.C.; 1994. Chavez B, Chavez-Brown M, Sopko Jr MA, Rey JA. Atypical antipsychotics in children with pervasive developmental disorders. Paediatr Drugs 2007;9(4):249–66. Cutler AJ, Montgomery SA, Feifel D, Lazarus A, Aström M, Brecher M. Extended release quetiapine fumarate monotherapy in major depressive disorder: a placebo- and duloxetine-controlled study. J Clin Psychiatry 2009;70:526–39. Findling RL, McNamara NK, Gracious BL, O' Riordan MA, Reed MD, Demeter C, et al. Quetiapine in nine youths with autistic disorder. J Child Adolesc Psychopharmacol 2004;14(2):287–94. Ghaziuddin M, Ghaziuddin N, Greden J. Depression in persons with autism: implications for research and clinical practice. J Autism Dev Disord 2002;32(4):299–306. Guy W. ECDEU assessment manual for psychopharmacology. Washington D.C., National Institute of Mental Health, U.S. Department of Health, Education and Welfare, 1976. Hellings JA, Kelley LA, Gabrielli WF, Kilgore E, Shah P. Sertraline response in adults with mental retardation and autistic disorder. J Clin Psychiatry 1996;57(8):333–6. King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD, et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior. Arch Gen Psychiatry 2009;66(6):583–90. Martin A, Koenig K, Scahill L, Bregman J. Open-label quetiapine in the treatment of children and adolescents with autistic disorder. J Child Adolesc Psychopharmacol 1999;9(2):99-107. McDougle CJ, Brodkin ES, Naylor ST, Carlson DC, Cohen DJ, Price LH. Sertraline in adults with pervasive developmental disorders: a prospective open label investigation. J Clin Psychopharmacol 1998;18(1):62–6.
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Olver JS, Ignatiadis S, Maruff P, Burrows GD, Norman TR. Quetiapine augmentation in depressed patients with partial response to antidepressants. Hum Psychopharmacol Clin Exp 2008;23:653–60. Pira L, Mongeau R, Pani L. The atypical antipsychotic quetiapine increases both noradrenaline and dopamine release in the rat prefrontal cortex. Eur J Pharmacol 2004;504:61–4. Savasir I, Sahin N. Application manual for the Wechsler Intelligence Scale for Children — Revised Edition (WISC-R). Ankara: Turkish Association of Psychologists; 1995. Schopler E, Reichler RJ, DeVellis RF, Daly K. Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). J Autism Dev Disord 1980;10(1):91-103. Steingard RJ, Zimnitzky B, DeMaso DR, Bauman ML, Bucci JP. Sertraline treatment of transition-associated anxiety and agitation in children with autistic disorder. J Child Adolesc Psychopharmacol 1997;7(1):9-15. Thase ME, Corya SA, Osuntokun O, Case M, Henley DB, Sanger TM, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry 2007;68(2):224–36.
Ali Evren Tufan Elazig Hospital for Mental Disorders, Department of Child Psychiatry, Rizaiye Mah., Mehmet Guclu Str., No: 71, Elazig, 23100, Turkey Corresponding author. Tel.: +90 424 218 10 83; fax: +90 424 2127831. E-mail address: [email protected]. Hüseyin Kutlu Kocaeli University Medical Faculty, Department of Psychiatry, Turkey 3 June 2009
Contents lists available at ScienceDirect
Progress in Neuro-Psychopharmacology & Biological Psychiatry j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p n p
Letter to the Editor (Case report) Adjunctive quetiapine may help depression comorbid with pervasive developmental disorders
1. Introduction Depression is probably the most common psychopathology accompanying pervasive developmental disorders (PDD) however; relatively few reports have focused on its phenomenology and treatment (Ghaziuddin et al., 2002). Sertraline hydrochloride and quetiapine fumarate were used individually in this population for the treatment of self-injurious and repetitive behaviors, aggression, irritability, and transition induced anxiety and agitation (Chavez et al., 2007; Findling et al., 2004; Hellings et al., 1996; Martin et al., 1999; McDougle et al., 1998; Steingard et al., 1997). Quetiapine, though, is reported to have poor efficacy and/or tolerability and, reports of the use of either of these drugs to treat depression accompanying PDD are limited (Findling et al., 2004; Martin et al., 1999). Additionally, combined use of sertraline and quetiapine for depression in this population has not been reported up to now. Here; we report the successful treatment of major depressive disorder (MDD) and associated self-injurious behavior in an adolescent with Pervasive Developmental Disorder — Not Otherwise specified (PDD-NOS) and Moderate Mental Retardation (MR) with a combination of sertraline hydrochloride and quetiapine fumarate. 2. Case report A 17 year-old girl was brought to our department with complaints of “insomnia, tearfulness, irritability and, loss of appetite”. The complaints had been present for the past 6 months and she also started to display self-injurious behavior (i.e. head-banging). Daily functioning, verbal output and appetite were reduced. Sexualized behaviors, increased energy and verbal output or hyperactivity were not present, either before, or along with the complaints. The symptoms were not associated with menstruation or attributable to changes in routine. Information about stressors and/or abuse was absent. The patient was diagnosed with Autistic Disorder when she was 4 years old. The mother was diagnosed and successfully treated for an MDD with sertraline when the patient was 3 years old. She was still receiving sertraline 14 years later at the time of her daughter's consultation. Physical and neurological examinations and laboratory tests at the time of application were within normal limits. Wechsler Intelligence Scale for Children–Revised Edition (WISC-R) revealed a full-scale I.Q of 41 (Moderate MR) (Savasir and Sahin, 1995). At the initial evaluation the CGI-S score was judged to be 5 (“significantly impaired”) and an evaluation with Childhood Autism Rating Scale (CARS) demonstrated a score of 36 (mild–moderate autistic symptoms) (Guy, 1976; Schopler et al., 1980). She was diagnosed with Major Depressive Disorder, Single Episode and PDD-NOS according to DSM-IV-TR criteria and started on sertraline 25 mg/day (APA, 1994). Quetiapine 25 mg/day was added to control self-injurious behavior and for night-time sedation. At weekly 0278-5846/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2009.09.009
visits, sertraline was titrated to 50 mg/day and quetiapine 100 mg/day in divided doses, respectively. The presenting symptoms started to reduce at the first month of treatment and the patient returned to baseline functioning at the end of 3rd month; with the CGI-I subscale being much improved. No side effects were reported within the treatment period. Though the core symptoms (verbal and nonverbal communication, relating to people) did not change the last CARS evaluation at the 3rd month revealed a score of 33 with improvements in the “adjustment to change” and “fear or irritability” domains. Monthly visits up to the ninth month of treatment did not demonstrate any significant gains, therefore the drugs were discontinued. After discontinuation of drugs, telephone follow-ups at three month intervals were provided to the family and three years after the index episode, the patient remains free of depressive symptoms while continuing to receive supportive therapy which began at the 3rd month of treatment. 3. Discussion Here, we report the successful treatment of depression and associated self-injurious behavior in an adolescent female with PDDNOS and Moderate MR with sertraline hydrochloride and quetiapine fumarate. Sertraline was previously studied in patients with PDD in three open-label studies and in all of those studies, similar to our patient, sertraline was well tolerated with minimal side effects (Hellings et al., 1996; McDougle et al., 1998; Steingard et al., 1997). The findings that sertraline also helped increase adjustment to change along with depressive symptoms and that treatment gains were maintained in the three year follow-up of our patient are interesting and need to be replicated. Quetiapine was studied in two open-label studies on patients with PDD in dosages that ranged from 100 to 750 mg/day with about 25 to 33% of the patients being classified as treatment responders after treatments of 12 to 16 weeks (Findling et al., 2004; Martin et al., 1999). The fact that our patient did not experience any significant side effects while benefiting from treatment may be explained by differing dosing strategies, the diagnosis of PDD-NOS, drug naivety or gender. Much interest has been generated in using quetiapine in depression following reports of its use as an augmentative agent (Olver et al., 2008). Recently, quetiapine monotherapy at the doses of 150 mg and 300 mg/ day was found to be effective, safe and tolerable in the treatment of patients with MDD, with onset of symptom improvement demonstrated at the first week (Cutler et al., 2009). The mechanism of action of the quetiapine antidepressant response remains speculative and may be due to increased levels of dopamine or noradrenaline (Pira et al., 2004) in the brain or, alternatively it may be a non-specific effect of atypical antipsychotics (Thase et al., 2007). 4. Conclusion Considering all factors, our results suggest that quetiapine and sertraline may help depression accompanying PDD. However, this antidepressant effect can be due to quetiapine, sertraline or their
Letter to the Editor (Case report)
combination. In the light of recent studies which do not support the use of SSRIs in this population (King et al., 2009), our results should be deemed preliminary and be replicated with further studies.
References American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th Ed. American Psychiatric Association: Washington D.C.; 1994. Chavez B, Chavez-Brown M, Sopko Jr MA, Rey JA. Atypical antipsychotics in children with pervasive developmental disorders. Paediatr Drugs 2007;9(4):249–66. Cutler AJ, Montgomery SA, Feifel D, Lazarus A, Aström M, Brecher M. Extended release quetiapine fumarate monotherapy in major depressive disorder: a placebo- and duloxetine-controlled study. J Clin Psychiatry 2009;70:526–39. Findling RL, McNamara NK, Gracious BL, O' Riordan MA, Reed MD, Demeter C, et al. Quetiapine in nine youths with autistic disorder. J Child Adolesc Psychopharmacol 2004;14(2):287–94. Ghaziuddin M, Ghaziuddin N, Greden J. Depression in persons with autism: implications for research and clinical practice. J Autism Dev Disord 2002;32(4):299–306. Guy W. ECDEU assessment manual for psychopharmacology. Washington D.C., National Institute of Mental Health, U.S. Department of Health, Education and Welfare, 1976. Hellings JA, Kelley LA, Gabrielli WF, Kilgore E, Shah P. Sertraline response in adults with mental retardation and autistic disorder. J Clin Psychiatry 1996;57(8):333–6. King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD, et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior. Arch Gen Psychiatry 2009;66(6):583–90. Martin A, Koenig K, Scahill L, Bregman J. Open-label quetiapine in the treatment of children and adolescents with autistic disorder. J Child Adolesc Psychopharmacol 1999;9(2):99-107. McDougle CJ, Brodkin ES, Naylor ST, Carlson DC, Cohen DJ, Price LH. Sertraline in adults with pervasive developmental disorders: a prospective open label investigation. J Clin Psychopharmacol 1998;18(1):62–6.
1571
Olver JS, Ignatiadis S, Maruff P, Burrows GD, Norman TR. Quetiapine augmentation in depressed patients with partial response to antidepressants. Hum Psychopharmacol Clin Exp 2008;23:653–60. Pira L, Mongeau R, Pani L. The atypical antipsychotic quetiapine increases both noradrenaline and dopamine release in the rat prefrontal cortex. Eur J Pharmacol 2004;504:61–4. Savasir I, Sahin N. Application manual for the Wechsler Intelligence Scale for Children — Revised Edition (WISC-R). Ankara: Turkish Association of Psychologists; 1995. Schopler E, Reichler RJ, DeVellis RF, Daly K. Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). J Autism Dev Disord 1980;10(1):91-103. Steingard RJ, Zimnitzky B, DeMaso DR, Bauman ML, Bucci JP. Sertraline treatment of transition-associated anxiety and agitation in children with autistic disorder. J Child Adolesc Psychopharmacol 1997;7(1):9-15. Thase ME, Corya SA, Osuntokun O, Case M, Henley DB, Sanger TM, et al. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry 2007;68(2):224–36.
Ali Evren Tufan Elazig Hospital for Mental Disorders, Department of Child Psychiatry, Rizaiye Mah., Mehmet Guclu Str., No: 71, Elazig, 23100, Turkey Corresponding author. Tel.: +90 424 218 10 83; fax: +90 424 2127831. E-mail address: [email protected]. Hüseyin Kutlu Kocaeli University Medical Faculty, Department of Psychiatry, Turkey 3 June 2009