Letter to the Editor
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 24, Number x, 2014 ª Mary Ann Liebert, Inc. Pp. 1–2 DOI: 10.1089/cap.2014.0065
Isoniazid-Induced Psychosis with Obsessive-Compulsive Symptoms (Schizo-Obsessive Disorder) in a Female Child Muharrem Burak Baytunca, MD, Serpil Erermis, MD, Tezan Bildik, MD, and Bu¨lent Kayahan, MD
To The Editor:
formed, including complete blood count, basic metabolic profile, and organic acid tests, which were within normal limits. Her cranial magnetic resonance imaging and electroencephalography were also normal. Her mental and motor milestones had been normal. There was no history of trauma, surgery, or any other physical disorder. Her mother had been diagnosed with schizoaffective disorder previously, and had been given risperidone depot treatment. After the first examination, Yale Brown Obsessive Compulsive Scale (Y-BOCS) was administered (Goodman et al. 1989). Y-BOCS score was 30. Both risperidone 1 mg/day and fluoxetine 10 mg/day were started. Risperidone dose titrated up to 2 mg/day, and fluoxetine was titrated up to 20 mg/day within a week. The patient had acute dystonia, and risperidone was discontinued, with the patient switched to aripiprazole starting at 2.5mg/day, then titrated to 5 mg/day gradually. The patient’s psychotic symptoms totally disappeared in 2 months (INH treatment was in the 3rd month) and aripiprazole was discontinued after 1 year. Because of the schizoaffective disorder in the patient’s family, her clinical symptoms were not necessarily thought to be related to INH prophylaxis, and INH was not discontinued immediately, but the patient was followed for short periods. Obsessive compulsive disorder (OCD) symptoms were successfully treated with 30 mg/day fluoxetine over 2 years of follow-up (see Fig. 1).
T
uberculosis (Tbc) has been a common worldwide health problem for many years, leading to morbidity and mortality. Drugs that are being used widely in the treatment of tuberculosis may cause psychiatric conditions. Isoniazid (INH), which can be used as a prophylactic agent in initial treatment of Tbc, has associated with psychotic conditions, which has been reported in the literature. One of the putative theories about this effect of INH is monoamine oxidase inhibition, and the other is decreasing NMethyl-d-aspartate receptors (NMDA) caused by the oxidative stress side effect of INH. Although INH has been associated with psychosis in many reports in the literature, there are rare case reports about psychotic disorders with obsessive compulsive features and INH administration. In this article, we aimed to present a patient who developed psychotic disorder with obsessive compulsive features after administration of INH. Case Report An 11-year-old girl who had been previously mentally and physically healthy, was prediagnosed with tuberculosis after investigation of coughing, and was given 300 mg/day INH prophylaxis because of her purified protein derivative (PPD) positivity (18 mm). In the 2nd week of INH augmentation, she developed bizarre delusions and behaviors (wrapping her feces into a piece of paper in order to preserve it, holding her breath when she was coming out of a room and coming in to another room, making associations between the color of food and death, such as tha tgreen means coffin, white means shroud, and black means death, and, therefore, not eating anything), paranoid delusions, visual hallucinations, agressive obsessions, and touching/hoarding compulsions. She had also anxiety, social withdrawal, concentration difficulties, academic problems, and weight loss. She was admitted to the psychiatric inpatient unit. Her neurological and pediatric consultations were normal. Her routine laboratory tests were per-
0 2thweek [Isoniazid prophylaxis started [Sch and OCDsymptomps (treatment started)
Discussion OCD and schizophrenia (Sch), which can impair individuals’ quality of life severely, may be seen together, but their combination has not been formally classified as schizo-obsessive disorder (SOD) in American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-V) as of yet (American Psychiatric Association 2013). Much research in genetic, neuroimaging, pharmacological, and neuropsychological areas has been conducted to determine whether SOD is a clinical entity that is distinct from OCD and Sch (Aoyama et al. 2000; Patel et al. 2010;
2nd month [Loss of Sch symptoms
6th month [INH stopped
1th year [Antipsychotic stopped
2nd year [Full recovery (Loss of OCD)
FIG. 1. Timeline of the patient. The patient’s Clinical Global Impressions Scale - Improvement score (Guy et al. 1976) was 1 and her Yale Brown Obsessive Compulsive Scale (Y-BOCS) score was 3 at her last psychiatric examination. She was considered to have made a full recovery and is still continuing her treatment at the outpatient unit of the psychiatry clinic.
Child and Adolescent Psychiatry Department, School of Medicine, Ege University, Izmir, Turkey.
1
2
BAYTUNCA ET AL.
Pavurovsky et al. 2005; Swets et al. 2014). The comorbidity of obsessive compulsive symptoms (OCS) and Sch has been found in a range of 7.8–64% (Kayahan et al. 2005; Nolfe et al. 2010). On the other hand, it is important to stress that the prognosis for OCD plus Sch is worse than that for monosyndromic OCD or Sch (Kayahan et al. 2005). Our patient was diagnosed with OCD and Sch on the basis of DSM-V, but her clinical picture was more favorable for SOD. It should also be kept in mind that OCSs may continue even though psychotic features alleviate (Attademo et al. 2012). Because of the lack of a precise line between OCD and SOD, clinicians are usually late in starting antipsychotic agents, and waste their time with only standard OCD treatments, which are not adequately effective in SOD. Anti-Tbc drugs have been shown to be precipitating factors for psychiatric disorders such as psychotic conditions, in many case reports and research reports. Those drugs are being used widely in prophylaxis and/or treatment of Tbc, which had 8,700,000 new cases and caused 1,400,000 deaths in 2011 (World Health Organization 2012; Doherty et al. 2013). INH still remains one of first-line drugs in Tbc (Ayieko et al. 2014), even though it has been well recognized that INH caused the adverse effects of several psychiatric conditions, such as suicide attemps, mania, depression, anxiety, or acute psychosis. According to present literature, SOD had not been reported before (Bhatia 1990; Abouesh et al. 2002; Ayieko et al. 2014). The mechanism of INH-induced acute psychotic symptoms or OCSs are not well understood. One of the putative effects of INH is to function as a monoamine oxidase inhibitor (MAOI), which cause degradation of serotonin and catecholamines, which are basic neurochemicals of Sch and OCD. Another assumption is that INH-induced depletion of pyridoxal phosphate, which is an important coenzyme in neurotransmitter metabolism, may cause reduced levels of dopamine, serotonin, and noradrenaline (Kass and Shandera 2010). NMDA receptors are suggested to be involved in both Sch and OCD pathophysiology, and it is also claimed that INH and its metabolites may cause oxidative stress, which can cause decreased levels of NMDA-2 in the hippocampus (Cicek et al. 2005; Richter et al. 2012). Withdrawal of INH may help in the resolution of symptoms via this NMDA hypothesis, but pyridoxine supplementation is not a good option (Kass and Shandera 2010). In this article, we aimed to make physicians aware of the rare adverse effect ‘‘SOD’’ of INH. Disclosures No competing financial interests exist. References Abouesh A, Stone C, Hobbs WR: Antimicrobial-induced mania (antibiomania): A review of spontaneous reports. J Clin Psychopharmacol 22:71–81, 2002. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013. Aoyama F, Iida J, Inoue M, Iwasaka H, Sakiyama S, Hata K, Kishimoto T: Brain imaging in childhood- and adolescence-onset schizophrenia associated with obsessive-compulsivesymptoms. Acta Psychiatr Scand 102:32–37, 2000.
Attademo L, De Giorgio G, Quartesan R, Moretti P: Schizophrenia and obsessive-compulsive disorder: from comorbidity to schizoobsessive disorder. Riv Psichiatr 47:106–115, 2012. Ayieko J, Abuogi L, Simchowitz B, Bukusi EA, Smith AH, Reingold A: Efficacy of isoniazid prophylactic therapy in prevention of tuberculosis in children: A meta-analysis. BMC Infect Dis 20;14:91, 2014. Bhatia MS: Isoniazid-induced obsessive compulsive neurosis. J Clin Psychiatry 51:387, 1990. Cicek E, Sutcu R, Gokalp O, Yilmaz HR, Ozer MK, Uz E, Ozcelik N, Delibas N: The effects of isoniazid on hippocampal NMDA receptors: protective role of erdosteine. Mol Cell Biochem 277:131–135, 2005. Doherty AM, Kelly J, McDonald C, O’Dywer AM, Keane J, Cooney J: A review of the interplay between tuberculosis and mental health. Gen Hosp Psychiatry 35: 398–406, 2013. Goodman WK, Price LH, Rausmussen SA: The Yale–Brown Obsessive Compulsive Scale (Y-BOCS). Part I: Development, use and reliability. Arch Gen Psychiatry 46:1006–1011, 1989. Guy W: ECDEU Assessment Manual for Psychopharmacology. Washington, DC: U.S. Department of Health, Education and Welfare; 1976. Kass JS, Shandera WX: Nervous system effects of antituberculosis therapy. CNS Drugs 24:655–657, 2010. Kayahan B, Ozturk O, Veznedaroglu B, Eraslan D: Obsessivecompulsive symptoms in schizophrenia: Prevalance and clinical correlates. Psychiatry Clin Neurosci 59:291–295, 2005. Nolfe G, Milano W, Zontini G, Petrella C, De Rosa M, Rundle–Smith S, Nolfe G: Obsessive-compulsive symptoms in schizophrenia: their relationship with clinical features and pharmacological treatment. J Psychiatr Pract 16:235–242, 2010. Patel DD, Laws KR, Padhi A, Farrow JM, Mukhopadhaya K, Krishnaiah R, Fineberg NA: The neuropsychology of the schizoobsessive subtype of schizophrenia: A new analysis. Psychol Med 40:921–933, 2010. Poyurovsky M, Kriss V, Weisman G, Faragian S, Schneidman M, Fuchs C, Weizman A, Weizman R: Familial aggregation of schizophreniaspectrum disorders and obsessive-compulsive associated disorders inschizophrenia probands with and without OCD. Am J Med Genet B Neuropsychiatr Genet 5:133:31–36, 2005. Richter MA, de Jesus DR, Hoppenbrouwers S, Daigle M, Deluce J, Ravindran LN, Fitzgerald PB, Daskalakis ZJ: Evidence for cortical inhibitory and excitatory dysfunction in obsessive compulsive disorder. Neuropsychopharmacology 37:1144–1151, 2012. Swets M, Dekker J, van Emmerik-van Oortmerssen K, Smid GE, Smit F, de Haan L, Schoevers RA: The obsessive compulsive spectrum in schizophrenia, a meta-analysis and meta-regression exploring prevalencerates. Schizophr Res 152:458–468, 2014. World Health Organization: Global Tuberculosis Report. Geneva, Switzerland: World Health Organization; 2012.
Address correspondence to: Muharrem Burak Baytunca, MD Child and Adolescent Psychiatry Department School of Medicine Ege University Bornova 35040, Izmir Turkey E-mail: [email protected]
JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 24, Number x, 2014 ª Mary Ann Liebert, Inc. Pp. 1–2 DOI: 10.1089/cap.2014.0065
Isoniazid-Induced Psychosis with Obsessive-Compulsive Symptoms (Schizo-Obsessive Disorder) in a Female Child Muharrem Burak Baytunca, MD, Serpil Erermis, MD, Tezan Bildik, MD, and Bu¨lent Kayahan, MD
To The Editor:
formed, including complete blood count, basic metabolic profile, and organic acid tests, which were within normal limits. Her cranial magnetic resonance imaging and electroencephalography were also normal. Her mental and motor milestones had been normal. There was no history of trauma, surgery, or any other physical disorder. Her mother had been diagnosed with schizoaffective disorder previously, and had been given risperidone depot treatment. After the first examination, Yale Brown Obsessive Compulsive Scale (Y-BOCS) was administered (Goodman et al. 1989). Y-BOCS score was 30. Both risperidone 1 mg/day and fluoxetine 10 mg/day were started. Risperidone dose titrated up to 2 mg/day, and fluoxetine was titrated up to 20 mg/day within a week. The patient had acute dystonia, and risperidone was discontinued, with the patient switched to aripiprazole starting at 2.5mg/day, then titrated to 5 mg/day gradually. The patient’s psychotic symptoms totally disappeared in 2 months (INH treatment was in the 3rd month) and aripiprazole was discontinued after 1 year. Because of the schizoaffective disorder in the patient’s family, her clinical symptoms were not necessarily thought to be related to INH prophylaxis, and INH was not discontinued immediately, but the patient was followed for short periods. Obsessive compulsive disorder (OCD) symptoms were successfully treated with 30 mg/day fluoxetine over 2 years of follow-up (see Fig. 1).
T
uberculosis (Tbc) has been a common worldwide health problem for many years, leading to morbidity and mortality. Drugs that are being used widely in the treatment of tuberculosis may cause psychiatric conditions. Isoniazid (INH), which can be used as a prophylactic agent in initial treatment of Tbc, has associated with psychotic conditions, which has been reported in the literature. One of the putative theories about this effect of INH is monoamine oxidase inhibition, and the other is decreasing NMethyl-d-aspartate receptors (NMDA) caused by the oxidative stress side effect of INH. Although INH has been associated with psychosis in many reports in the literature, there are rare case reports about psychotic disorders with obsessive compulsive features and INH administration. In this article, we aimed to present a patient who developed psychotic disorder with obsessive compulsive features after administration of INH. Case Report An 11-year-old girl who had been previously mentally and physically healthy, was prediagnosed with tuberculosis after investigation of coughing, and was given 300 mg/day INH prophylaxis because of her purified protein derivative (PPD) positivity (18 mm). In the 2nd week of INH augmentation, she developed bizarre delusions and behaviors (wrapping her feces into a piece of paper in order to preserve it, holding her breath when she was coming out of a room and coming in to another room, making associations between the color of food and death, such as tha tgreen means coffin, white means shroud, and black means death, and, therefore, not eating anything), paranoid delusions, visual hallucinations, agressive obsessions, and touching/hoarding compulsions. She had also anxiety, social withdrawal, concentration difficulties, academic problems, and weight loss. She was admitted to the psychiatric inpatient unit. Her neurological and pediatric consultations were normal. Her routine laboratory tests were per-
0 2thweek [Isoniazid prophylaxis started [Sch and OCDsymptomps (treatment started)
Discussion OCD and schizophrenia (Sch), which can impair individuals’ quality of life severely, may be seen together, but their combination has not been formally classified as schizo-obsessive disorder (SOD) in American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-V) as of yet (American Psychiatric Association 2013). Much research in genetic, neuroimaging, pharmacological, and neuropsychological areas has been conducted to determine whether SOD is a clinical entity that is distinct from OCD and Sch (Aoyama et al. 2000; Patel et al. 2010;
2nd month [Loss of Sch symptoms
6th month [INH stopped
1th year [Antipsychotic stopped
2nd year [Full recovery (Loss of OCD)
FIG. 1. Timeline of the patient. The patient’s Clinical Global Impressions Scale - Improvement score (Guy et al. 1976) was 1 and her Yale Brown Obsessive Compulsive Scale (Y-BOCS) score was 3 at her last psychiatric examination. She was considered to have made a full recovery and is still continuing her treatment at the outpatient unit of the psychiatry clinic.
Child and Adolescent Psychiatry Department, School of Medicine, Ege University, Izmir, Turkey.
1
2
BAYTUNCA ET AL.
Pavurovsky et al. 2005; Swets et al. 2014). The comorbidity of obsessive compulsive symptoms (OCS) and Sch has been found in a range of 7.8–64% (Kayahan et al. 2005; Nolfe et al. 2010). On the other hand, it is important to stress that the prognosis for OCD plus Sch is worse than that for monosyndromic OCD or Sch (Kayahan et al. 2005). Our patient was diagnosed with OCD and Sch on the basis of DSM-V, but her clinical picture was more favorable for SOD. It should also be kept in mind that OCSs may continue even though psychotic features alleviate (Attademo et al. 2012). Because of the lack of a precise line between OCD and SOD, clinicians are usually late in starting antipsychotic agents, and waste their time with only standard OCD treatments, which are not adequately effective in SOD. Anti-Tbc drugs have been shown to be precipitating factors for psychiatric disorders such as psychotic conditions, in many case reports and research reports. Those drugs are being used widely in prophylaxis and/or treatment of Tbc, which had 8,700,000 new cases and caused 1,400,000 deaths in 2011 (World Health Organization 2012; Doherty et al. 2013). INH still remains one of first-line drugs in Tbc (Ayieko et al. 2014), even though it has been well recognized that INH caused the adverse effects of several psychiatric conditions, such as suicide attemps, mania, depression, anxiety, or acute psychosis. According to present literature, SOD had not been reported before (Bhatia 1990; Abouesh et al. 2002; Ayieko et al. 2014). The mechanism of INH-induced acute psychotic symptoms or OCSs are not well understood. One of the putative effects of INH is to function as a monoamine oxidase inhibitor (MAOI), which cause degradation of serotonin and catecholamines, which are basic neurochemicals of Sch and OCD. Another assumption is that INH-induced depletion of pyridoxal phosphate, which is an important coenzyme in neurotransmitter metabolism, may cause reduced levels of dopamine, serotonin, and noradrenaline (Kass and Shandera 2010). NMDA receptors are suggested to be involved in both Sch and OCD pathophysiology, and it is also claimed that INH and its metabolites may cause oxidative stress, which can cause decreased levels of NMDA-2 in the hippocampus (Cicek et al. 2005; Richter et al. 2012). Withdrawal of INH may help in the resolution of symptoms via this NMDA hypothesis, but pyridoxine supplementation is not a good option (Kass and Shandera 2010). In this article, we aimed to make physicians aware of the rare adverse effect ‘‘SOD’’ of INH. Disclosures No competing financial interests exist. References Abouesh A, Stone C, Hobbs WR: Antimicrobial-induced mania (antibiomania): A review of spontaneous reports. J Clin Psychopharmacol 22:71–81, 2002. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013. Aoyama F, Iida J, Inoue M, Iwasaka H, Sakiyama S, Hata K, Kishimoto T: Brain imaging in childhood- and adolescence-onset schizophrenia associated with obsessive-compulsivesymptoms. Acta Psychiatr Scand 102:32–37, 2000.
Attademo L, De Giorgio G, Quartesan R, Moretti P: Schizophrenia and obsessive-compulsive disorder: from comorbidity to schizoobsessive disorder. Riv Psichiatr 47:106–115, 2012. Ayieko J, Abuogi L, Simchowitz B, Bukusi EA, Smith AH, Reingold A: Efficacy of isoniazid prophylactic therapy in prevention of tuberculosis in children: A meta-analysis. BMC Infect Dis 20;14:91, 2014. Bhatia MS: Isoniazid-induced obsessive compulsive neurosis. J Clin Psychiatry 51:387, 1990. Cicek E, Sutcu R, Gokalp O, Yilmaz HR, Ozer MK, Uz E, Ozcelik N, Delibas N: The effects of isoniazid on hippocampal NMDA receptors: protective role of erdosteine. Mol Cell Biochem 277:131–135, 2005. Doherty AM, Kelly J, McDonald C, O’Dywer AM, Keane J, Cooney J: A review of the interplay between tuberculosis and mental health. Gen Hosp Psychiatry 35: 398–406, 2013. Goodman WK, Price LH, Rausmussen SA: The Yale–Brown Obsessive Compulsive Scale (Y-BOCS). Part I: Development, use and reliability. Arch Gen Psychiatry 46:1006–1011, 1989. Guy W: ECDEU Assessment Manual for Psychopharmacology. Washington, DC: U.S. Department of Health, Education and Welfare; 1976. Kass JS, Shandera WX: Nervous system effects of antituberculosis therapy. CNS Drugs 24:655–657, 2010. Kayahan B, Ozturk O, Veznedaroglu B, Eraslan D: Obsessivecompulsive symptoms in schizophrenia: Prevalance and clinical correlates. Psychiatry Clin Neurosci 59:291–295, 2005. Nolfe G, Milano W, Zontini G, Petrella C, De Rosa M, Rundle–Smith S, Nolfe G: Obsessive-compulsive symptoms in schizophrenia: their relationship with clinical features and pharmacological treatment. J Psychiatr Pract 16:235–242, 2010. Patel DD, Laws KR, Padhi A, Farrow JM, Mukhopadhaya K, Krishnaiah R, Fineberg NA: The neuropsychology of the schizoobsessive subtype of schizophrenia: A new analysis. Psychol Med 40:921–933, 2010. Poyurovsky M, Kriss V, Weisman G, Faragian S, Schneidman M, Fuchs C, Weizman A, Weizman R: Familial aggregation of schizophreniaspectrum disorders and obsessive-compulsive associated disorders inschizophrenia probands with and without OCD. Am J Med Genet B Neuropsychiatr Genet 5:133:31–36, 2005. Richter MA, de Jesus DR, Hoppenbrouwers S, Daigle M, Deluce J, Ravindran LN, Fitzgerald PB, Daskalakis ZJ: Evidence for cortical inhibitory and excitatory dysfunction in obsessive compulsive disorder. Neuropsychopharmacology 37:1144–1151, 2012. Swets M, Dekker J, van Emmerik-van Oortmerssen K, Smid GE, Smit F, de Haan L, Schoevers RA: The obsessive compulsive spectrum in schizophrenia, a meta-analysis and meta-regression exploring prevalencerates. Schizophr Res 152:458–468, 2014. World Health Organization: Global Tuberculosis Report. Geneva, Switzerland: World Health Organization; 2012.
Address correspondence to: Muharrem Burak Baytunca, MD Child and Adolescent Psychiatry Department School of Medicine Ege University Bornova 35040, Izmir Turkey E-mail: [email protected]
