Baseline lipid levels and acute treatment response to paroxetine and tianeptine in depressed women.
To the Editors: Treatment-resistant patients with schizophrenia are frequently prescribed clozapine and a number of authors have reported the possibility that clozapine produces, unmasks, or worsens obsessivecompulsive symptoms (OCS). Results from a recent placebo-controlled trial suggest that the combination of clozapine with aripiprazole in patients with schizophrenia is safe. We report on 2 patients who developed OCS after starting clozapine and whose OCS cleared after adding aripiprazole. The first patient is a 32-year-old single unemployed man with disorganized schizophrenia who failed to respond to several antipsychotics including chlorpromazine, clotiapine, haloperidol, quetiapine, and zuclopenthixol at therapeutical doses. The patient showed a very good response to clozapine (200 mg/d), except for the onset of obsessive thinking and control rituals. This patient did not endorse a history of obsessive thoughts or compulsive behaviors before starting clozapine. His persecutory delusions, bizarre behaviors, and hallucinations cleared approximately 4 weeks after starting clozapine. However, upon beginning clozapine, he started to experience intrusive and unpleasant thoughts that produced uneasiness and apprehension. Specifically, he started to experience thoughts about the possibility that his electric appliances in general, and the espresso machine in particular, would not work appropriately. He clearly understood and recognized that his impression were unreal; however, he felt that he had to act as if his thoughts were correct. He described those thoughts as unwanted, paralyzing, severe, and constantly present. He clearly differentiated such thoughts from the previously experienced delusional thoughts. Although he was able to recognize that the obsessive thoughts were irrational, he was unable to stop thinking about the coffee machine and the only way for him to decrease the anxiety was to call the repair service several times per day. When a patient presents with both psychotic and obsessive symptoms, it often is difficult to distinguish between schizophrenia, OCD with poor insight, schizophrenia comorbid with obsessive compulsive disorder, or schizophrenia comorbid with medication-induced obsessive symptoms. In our opinion, this patient endorsed the latter diagnosis. Given the concomitant presence of residual negative symptoms, we added aripiprazole 15 mg/d, which was then increased to 30 mg/d. Upon starting aripiprazole, the OCS gradually diminished until complete resolution after approximately 5 weeks. The second patient is a 39-year-old man with treatment-resistant schizoaffective disorder, who showed a relatively good response to a combination of lithium and clozapine (500 mg/d), except for the onset of obsessive thinking, possibly induced by clozapine. He described the obsessive thinking as involuntary, unpleasant, and seemingly uncontrollable thoughts of racist nature against black people, which caused severe anxiety and fear about possibly being unable to prevent himself from screaming those sentences in front of black persons. Differently from the previously experienced delusional thoughts, the thoughts were perceived and described as unfair, unreal, and unwanted, yet impossible to ignore. After failing low doses of selective serotonin reuptake inhibitors, which invariably triggered a mixed episode, with dysphoria, increase in substance use, and suicidal tendencies, aripiprazole was introduced (in combination with clozapine) at a dose of 15 mg and then titrated up to 30 mg/d, whereas clozapine was gradually reduced to 200 mg/d. Approximately 1 week after starting aripiprazole, the obsessive thoughts began to be less frequent and intense. The patient perceived and reported a clear improvement and went from spending almost the entire day fighting with those thoughts to spending no more than 1 to 2 hours per day thinking about racist issues and attempting to clear those unwanted thoughts out of his head. For the following months, the intensity and frequency of racist thoughts decreased. However, it took almost 1 year before the thoughts completely cleared, and the possibility that at least a part of the improvement be due to a natural remission of OCS over a prolonged period and/or to a dose reduction of clozapine should be considered. Our cases confirm other preliminary observations from other authors about the possible benefits of adding aripiprazole to clozapine to treat obsessive compulsive symptoms that are caused, triggered, or worsened by clozapine alone. Although a detailed description of the possible hypotheses beyond the exacerbation of OCSs by clozapine and its reversal by aripiprazole augmentation go beyond the scopes of this letter to the Editors, it is likely that serotonergicdopaminergic interactions play a role and that aripiprazole exerted its beneficial effect via its partial agonism at the D2 and dopamineand serotonin-stabilizing properties. Large, randomized, placebocontrolled trials to test the risks and benefits of this strategy are warranted.