Aripiprazole-induced obsessive-compulsive symptoms.

Aripiprazole is a novel antipsychotic with a unique pharmacological profile as a dopamine partial agonist. It is indicated for treatment of schizophrenia and bipolar disorder. This new antipsychotic has low rate of extrapyramidal side effects, metabolic changes and no significant adverse effect on serum prolactin concentration. In addition,it is not associated with significant weight gain like other atypical antipsychotics. As a reason, when other antipsychotics cause these adverse events, it's not uncommon to switch to Aripiprazole. Obsessive compulsive symptoms have been untoward sequel of a few second-generation antipsychotics. Among the second generation antipsychotics Clozapine, Olanzapine, and Risperidone are the most prominent agents associated with these sequelae, according to case reports. More recently, a handful of case reports indicated development of Obsessive-compulsive symptoms with Aripiprazole. We report a case that exhibited similar unexpected adverse effects after administration of Aripiprazole. Keywords: Aripiprazole, Second generation antipsychotics, Obsessive-compulsive symptoms (OCS). Copyright:

Aripiprazole is a D2 dopamine receptor partial agonist, a major differentiating pharmacologic feature compared to serotonin– dopamine antagonists. Due to its D2 partial agonist actions, aripiprazole is theoretically an atypical antipsychotic with reduced extrapyramidal side effects (EPS) and hyperprolactinemia. It has a partial agonistic activity on serotonin 5-HT1A receptors and an antagonistic activity on 5-HT2A receptors.[1] Aripiprazole is effective in treating schizophrenia and mania. It lacks the pharmacological properties normally associated with sedation, namely M1-muscarinic cholinergic and H1-histaminic antagonist properties, and thus, is not generally sedating. A major differentiating feature of aripiprazole is that it has little or no propensity for weight gain. Furthermore, there seems to be little association of aripiprazole with dyslipidemia, elevation of fasting triglycerides, or insulin resistance. In fact, when patients with weight gain and dyslipidemia caused by other antipsychotics are switched to aripiprazole, there can be weight loss and lowering of fasting triglyceride levels. The pharmacologic properties that make aripiprazole different in terms of its lower metabolic risk are unknown but could be explained if aripiprazole lacks the ability to bind to postulated receptors that mediate insulin resistance and hypertriglyceridemia.[23] To avoid relapse in patients with psychosis, it is important to continue antipsychotic treatment following stabilization of the patient after an acute episode. However, sometimes, relatively stable patients receiving maintenance therapy with another antipsychotic may need to switch to aripiprazole because of adverse effects. These may include EPS, weight gain, hyperglycemia, hyperlipidemia, cardiovascular conditions, and increased serum prolactin. Considered as having a favorable metabolic profile, aripiprazole could be viewed as an important factor for use in long-term treatment. In addition, the lack of sedative effects at clinically effective doses may help to motivate patients to continue maintenance therapy with aripiprazole.[4]

Emergence or exacerbation of obsessive–compulsive symptoms (OCS) during treatment with atypical antipsychotics has been extensively described in the literature.[56] It was noticed that a few antipsychotics can cause obsessive–compulsive like symptoms. Clozapine, olanzapine, and risperidone are the most prominent agents associated with OC symptoms.[7] However, there are only a few case reports of the appearance of OCS due to aripiprazole. We report a case that exhibited OCS after administration of aripiprazole for treatment of a psychotic disorder. A written informed consent was taken from the patient.

CASE REPORT

A 35-year-old female, who was a known case of unspecified nonorganic psychosis maintaining on risperidone 1 mg, reported for a regular follow-up. She was on risperidone for the past 6 years following postpartum psychosis. She also had a few relapses over the past years. Risperidone was gradually tapered over the years. During her follow-ups, she persistently complained of weight gain. Clinical examination and routine investigations were done to rule out other causes of weight gain and then risperidone was stopped, and she was started on tablet aripiprazole 5 mg. Following this, 3 weeks later, she reported to the outpatient department with complaints of having distressing thoughts and impulses to hit and kill her children. She also mentioned that she has been throwing rods, sticks, and sickle out of her home, as she was worried that she might harm her children. These thoughts and impulses were persistent and intrusive. She considered them as irrational, inappropriate, and they caused a lot of distress in her. She also claimed that they were her own thoughts and could not ignore or suppress them though she tried. No other obsessive–compulsive symptoms were noticed or reported. She had no past history of similar symptoms and no family history of psychiatric disorders. She had no significant medical history. On mental status examination, she was found to have no active psychotic symptoms. The patient was evaluated with routine investigations and magnetic resonance imaging of the brain, which were within normal limits.

Aripiprazole was stopped and escitalopram 10 mg was started to treat the obsessive symptoms. Risperidone was started again in view of her previous response and increased to 2 mg. Over 2 weeks, the patient reported of significant improvement. Over 6 weeks, escitalopram was gradually tapered and stopped and she was continued only on risperidone. When she reported for follow-up after 4 weeks, she had no obsessive–compulsive or psychotic symptoms. She was advised dietary and lifestyle modifications and regular exercises for the management of her weight.

DISCUSSION

This case reports a rare instance in which administration of a partial dopamine agonist, aripiprazole, during treatment of psychosis, induced obsessive–compulsive thoughts and impulses. These symptoms were not related to psychosis, as she did not have similar symptoms in the past, and there was no new emergence of psychotic symptoms. Moreover, features were suggestive of obsessive symptoms. Furthermore, the time relationship between aripiprazole administration and the development of obsessive thoughts and impulses supports its causative role. In addition, routine investigations and neuroimaging were done to rule out organic causes for the newly emerged symptoms, and all were found to be within normal limits. Therefore, obsessive thoughts and impulses in the present case are not considered as part of psychosis or result of any organic disorder.

Previous case reports indicate that most second-generation antipsychotics (SGAs) have been implicated in the de novo emergence and exacerbation of OCS in patients with schizophrenia, despite having anti-obsessional effects. Among SGAs, clozapine, olanzapine, and risperidone are the most commonly involved drugs.[7] Clozapine confers the greatest risk of OCS in schizophrenia, with 20%–28% of clozapine-treated patients experiencing de novo OCS and 10%–18% incurring an exacerbation of preexisting OCS, followed by olanzapine with 11%–20%.[7] Only a very few previous case reports have shown obsessive–compulsive-related symptoms in use of other atypical antipsychotic, especially aripiprazole. Aripiprazole is the new generation atypical antipsychotic that is a “dopamine system stabilizer.” There is recent evidence for a beneficial effect of aripiprazole in obsessive–compulsive disorder (OCD).[8] However, more recently, a few case reports indicated worsening and emergence of OCS during treatment with aripiprazole. Previous case reports showed that aripiprazole, during treatment of a bipolar disorder, induced behavioral changes related to impulse control and excessive shopping.[9] A case of hypersexuality induced by aripiprazole has been reported.[10] Another case report indicated that the introduction of aripiprazole caused the development of an irresistible urge to gamble and also experienced a compulsion to eat. The urge to gamble stopped 1 month after switching to ziprasidone 40 mg twice a day.[11]

The serotonergic (5-HT) system is known to play a major role in OCD, and selective serotonin reuptake inhibitors are effective agents in the treatment of OCD. The neurobiological mechanisms of antipsychotic-induced OCS have been hypothetical and definitive explanations are yet to come. Any attempt to explain the neurobiological mechanism is also complicated by the paradox of therapeutic improvement noted with atypical antipsychotics in OCD patients with or without comorbid psychosis.[12] The 5-HT2A and 5-HT2C receptor antagonism has been postulated to play a role in the generation of OCS in patients who are treated with clozapine in psychotic disorders.[1314] Furthermore, 5-HT2C receptors have been found in greater number in the basal ganglia,[15]an area that has been linked to OCD in many imaging studies. However, given the complexity of the numerous 5-HT receptor systems, it is unlikely that 5-HT2 receptor antagonism alone can account for antipsychotic-induced OCS because, for example, more cases of olanzapine-induced OCS would be expected on the basis of its receptor profile.[12] There could be a possible role of dopamine as well.[16] In fact, a higher 5HT 2/D2 antagonism, especially at lower doses, has been hypothesized to be one possible obesogenic mechanism.[12] Support for this hypothesis could be drawn from the fact that clozapine, olanzapine, quetiapine, and risperidone possess the same property, but haloperidol, with a very low 5HT2/D2 ratio,[17]has not been shown to induce or exacerbate OCD so far. It is important to note that aripiprazole also has higher 5HT2/D2 antagonism owing to its full antagonistic action on 5HT2 and partial agonistic action on D2 receptors. Aripiprazole's action via 5HT2c, D3 receptors and antagonism of 5HT6 and 5HT7 serotonin receptors are still unknown[18]which could have potential roles to play.[19] Basic neuroscience research should now systematically investigate the obesogenic property of atypical antipsychotics. However, further careful evaluation is required to elucidate mechanisms through which aripiprazole causing obsessive–compulsive symptoms.

CONCLUSION

Although aripiprazole is a new antipsychotic with a low risk of adverse effects, its distinctive feature as a dopamine partial agonist could cause unexpected side effects. It is necessary to pay additional attention and monitor for such adverse effects. Clinicians need to be vigilant for aripiprazole-induced OCS and consider appropriate treatment strategies for these symptoms when they become a clinical concern.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.