Isotretinoin (Accutane) ranks in the top 10 of the US Food and Drug Administration's database of drugs associated with reports of depression and suicide attempts. However, this association is still controversial because up to 5.6% of patients with moderate acne may have pre-existing suicidal ideations, improvement of acne often reduces associated depression, and isotretinoin users are reportedly no more likely than those taking antibiotics for acne to have depression or commit suicide. We describe a series of cases of manic psychosis that developed in a 1-year period (2003) in association with isotretinoin treatment and resulted in suicidality and progression to long-standing psychosis. Cases were drawn from 500 soldiers who had been evaluated in a military specialists dermatology clinic for severe acne. Data were summarized from medical records of five severe acne patients treated by isotretinion during their compulsory military service. Data from their draft board examinations and service records, as well as repeated clinical assessments by certified psychiatrists at the Israel Defense Forces (IDF) Mental Health Department clinic, were evaluated. Five young adults developed manic psychosis within a mean of 7.6 months of exposure to isotretinoin. In three cases, this was accompanied by a suicide attempt, and in three cases, psychosis lasted for longer than 6 months. Either a personal history of obsessive-compulsive disorder, neurological insult or family history of a major psychiatric illness were present in all cases. The present case-series is suggestive of an increase in the likelihood of an association between exposure to isotretinion and manic psychosis. Associated risk factors were both family and personal history of psychiatric morbidity. Further studies are needed to establish our findings.

The use of typical antipsychotics is limited in children with schizophrenia, owing to the high rate of response failure and early appearance of extrapyramidal syndromes as well as tardive and withdrawal dyskinesia. The aim of the present study was to examine the effectiveness of the atypical antipsychotic olanzapine in the treatment of childhood-onset schizophrenia. The study sample included nine children hospitalized for schizophrenia who had proven refractory to treatment with at least two antipsychotic drugs. Olanzapine was administered after a 2-week washout period in gradually increasing doses to a maximum of 5 mg/day on day 5 and 10 mg/day in week 3; six patients received up to 20 mg/day as of week 5. The duration of the study was 12 weeks. Patient psychiatric status was measured with three scales at onset of therapy and thereafter once weekly. Patients also underwent regular blood, laboratory, and liver function tests, and we also monitored their blood pressure and weight and performed electrocardiography and electroencephalography. A reduction in all psychopathology scores was obtained at 12 weeks from baseline. All extrapyramidal symptoms of previous medications resolved, and there were no new incidents. Side effects were mild. There were no adverse changes in blood chemistry, hematological tests, or electrocardiography parameters, but the treatment was associated with a significant weight gain (6.10 +/- 3.25 kg). At 1-year follow-up, the improvement in psychiatric symptoms was sustained in eight children. We conclude that olanzapine may have potential as a first-line drug in the treatment of drug-resistant childhood-onset schizophrenia. Large-scale, double-blind, placebo-controlled comparative studies are needed to clarify the role of the various atypical antipsychotics in both treatment-resistant and treatment-naïve populations with psychotic symptoms/disorders.

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