A 42 year-old man with a past medical history of schizoaffective disorder, hyperlipidemia, and gastrointestinal reflux disease was admitted to an adult psychiatric unit secondary to intrusive thoughts that were sexual, homicidal, and suicidal in nature. Similar thoughts with tics were first reported 2 decades prior to the current hospital admission; however symptoms of depression were most prominent then and he was initially diagnosed with only major depressive disorder. During the following years there were documented reports of “paranoia and delusions related to contamination” as well as continued reports of intrusive violent thoughts also believed to be delusions. This led to a diagnosis of schizoaffective disorder; and antipsychotics became the primary modality of treatment over the next decade. Documented antipsychotics trials included aripiprazole, olanzapine, lurasidone, and quetiapine, all of which were associated with a lack of adequate improvement or adverse events. Records indicated that haloperidol combined with fluvoxamine did result in partial improvement. Antidepressants were also utilized intermittently over this 20-year period to target mood symptoms. Historically, the antidepressant trial with the highest documented relative dose was paroxetine 60 mg. It was during this time period with paroxetine that there was documented improvement of the patient's intrusive thoughts. Side effects limited use of the paroxetine 60 mg, and after it was decreased the violent intrusive thoughts worsened.\nInevitably the patient's outpatient provider after years of suboptimal response to antipsychotics initiated clozapine to target what was continued to be described as psychotic symptoms in the medical record. However, as the clozapine was gradually increased to 400 mg the patient noted a severe worsening of intrusive thoughts causing secondary depressed mood, anxiety, and suicidal ideation leading to hospitalization at our facility. It was during this admission that there was exploration of the patient's intrusive thoughts, which were clearly obsessions in that they were persistent, unwanted, egodystonic thoughts. Efforts by the patient to suppress or ignore these thoughts were futile, resulting in significant anxiety and distress. Yet while these obsessions occupied a significant amount of time during the day, impacting his social and work functioning, he denied any ritualistic behaviors or compulsions. Family history was found to be positive for an aunt and mother with hoarding disorder and a cousin with OCD. As the obsession were not attributable to the use of substances, a medication condition, or other mental disorders, the diagnosis of OCD was given for the first time based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition []. With the patient now diagnosed with OCD, he was appropriately treated; and there was a plan to initiate fluoxetine with a goal dose of 80 mg. Given the historical nature of the schizoaffective diagnosis, clozapine was continued taking into account there had been improvement during the hospitalization and that it would need to be slowly tapered as an outpatient to avoid adverse effects. The patient was safely discharged with minimal intrusive thoughts and it was recommended to the patient's outpatient provider that clozapine be discontinued after a slow taper. However, in the following months, the patient's outpatient provider had increased clozapine to 700 mg. This was associated again with a subsequent worsening and exacerbation of distressing intrusive thoughts leading to another hospitalization. Serum clozapine and norclozapine levels upon admission were found to be 453 ng/mL and 464 ng/mL, respectively. Clozapine was rapidly discontinued due to the association with OCS, as well as the patient's clinical presentation after each clozapine escalation. Clozapine was tapered over approximately 2 weeks without complications such as cholinergic rebound, catatonia, serotonin syndrome, or withdrawal dyskinesias [–]. More importantly there was no emergence of psychotic symptoms, strengthening the likelihood that the patient did not have schizoaffective disorder based on DSM-5 criteria.\nIn review of records and after discussion with the patient, it was determined that the past fluvoxamine trial did not reach an adequate dose for the treatment of OCD. Fluvoxamine was started and increased to 200 mg after clozapine had been allowed to wash out. Low-dose aripiprazole was also initiated to augment the fluvoxamine given the severity of the presentation, the benefits of this antipsychotic in treatment resistant OCD, and the low risk of inducing OCS []. The patient was discharged with resolution of intrusive thoughts and improvement in mood and still without emergence of psychotic symptoms. Following this hospitalization the patient began to see a therapist who specialized in exposure and response prevention therapy to address his OCD. Longitudinally, the patient struggled with depression and anxiety associated with residual obsessions resulting in fluvoxamine being changed to clomipramine. The last known dose of clomipramine was 150 mg and reported as having reasonable control of OCS as an outpatient. Up to a year following the second reported hospitalization at our facility there were no patient reports or documentation noted of criteria sufficient for a diagnosis of schizoaffective disorder or other psychotic disorders.
Ms. A, a 40-year-old woman diagnosed with a residual schizophrenia [] was admitted following an exacerbation of psychotic symptoms with a predominance of anxiety despite 700 mg/d of clozapine for two years. The clinical scores and the trough plasma concentrations of clozapine and norclozapine at admission were CGI : 5; total PANSS: 123; positive: 17/49; negative: 18/49; excited component: 12/35; general: 39/112; Hamilton-anxiety: 14/56; clozapine: 896 ng/mL; norclozapine: 551 ng/mL, respectively (clozapine therapeutic range: 350–600 ng/mL [–]). Because of the risks of seizures, the dose was reduced to 500 mg/d, and aripiprazole (10 mg/d) was added. Clozapine and norclozapine plasma concentrations measured after 10 days were decreased according to the reduction of the dose (615 ng/mL and 478 ng/mL, resp.). The aripiprazole plasma concentration after 10 days was 282 ng/mL. Following a clinical reduction of the anxiety, the patient was discharged from the hospital three weeks after the addition of aripiprazole.\nA followup over 6 months did not reveal any change in the CGI and PANSS scores (at 6 months: CGI : 5; total PANSS: 125; positive: 18/49; negative: 23/49; excited component 10/35; general: 38/112). On the other hand, the Hamilton-anxiety score diminished progressively to 12, 7, and 8 after one, three, and 6 months, respectively. Clozapine and norclozapine plasma levels were stable over this period (at the sixth month: 608 ng/mL, 443 ng/mL, and 75 kg, resp.), and the comedications (clorazepate 20 mg/d, valsartane 40 mg/d, zopiclone 7,5 mg/d, and tamsulosine 0.4 mg/d) were not modified. No reports are describing an impact on anxiety by the antihypertensive comedication by valsartane (an angiotensin II receptor antagonist) and tamsulosine (peripheral α1-antagonist). There is no significant pharmacokinetic or pharmacodynamic interactions of that comedication and the antipsychotic/anxiolytic treatments.