INTRODUCTION
Aripiprazole is an atypical antipsychotic which differentiated from the other atypical antipsychotic drugs due to partial agonistic effect on presynaptic dopamine D2 autoreceptor. At the same time, antagonistic effect on postsynaptic D2 dopamine receptor is available (1). For this reason, aripiprazole affects like agonist in the absence of dopamine and it affects like antagonist in the presence of excessive dopamine. Aripiprazole is used to treat a number of psychiatric conditions, including schizophrenia, bipolar disorder, and major depressive disorder. Although aripiprazole is a well tolerated antipsychotic, some side effect such as headache, insomnia, agitation, anxiety, akatizi may occur during the usage (2). While almost all second generation antipsychotics-induced mania/hypomania are reported, aripiprazol-induced mania/hipomania has been reported as very rare (3). In this article, we will disscuss a case which was diagnosed with paranoid schizophrenia for 20 years and developed mania after suggesting 30mg/day aripiprazole treatment.
CASE
M.D., 41 years old, primary school graduated, housewife, married for 20 years, mother of two, was born in Rize, still lives with her family in Rize. Patient who took her own oral antidiabetic medication in order to attempt suicide was taken to our hospital emergency services by her relatives and she hospitalized in our clinic after follow-up in the emergency department.
History: The patient who applied to a psychiatry outpatient clinic with the complaints of being cheated by her husband, thinking that her neighbours talk about her, thinking to harm herself, hearing voices, laughing and talking to herself, introversion and insomnia symptoms was diagnosed with paranoid schizophrenia and treated with haloperidol and biperiden 20 years ago. However, she did not use the medications on a regular basis. In the follow-up period she was hospitalized for tree times and she used antipsychotics such as chlorpromazine, risperidone, haloperidol, quetiapin, flupentiksole, ziprasidone. But she saw the most benefit from risperidone. A year ago, due to the increase in similar complaints she was hospitalized in our clinic for 47 days and 6mg/day of risperidone treatment was suggested. After discharge she was suggested risperidone consta with 50mg/15day (IM). However, on outpatient monitoring her treatment was replaced with 12mg/day of paliperidone due to patient’s ongoing complaints. The patient who took paliperidon for 9 month and not get well was taken to a different hospital by her relatives. Her treatment was created again as 6mg/day of risperidone and risperidone consta 50mg/15days (IM). However, because of high level of prolactin (219ng/ml), oral form of risperidone dose was decreased while aripiprazole treatment was started and increased gradually. After aripiprazole dosage of 30mg/day some symptoms like hiperactivity, increase in the amount of speech and energy and sexual interest, insomnia, costume-outfit changes were occured. The patient observed an increase in her apatite begun to discuss with her husband about her diet frequently. After a discussion like this she took her own oral antidiabetic drugs in order to suicide and were brought to our hospital. She hospitalized for second time.
Self and family history: She was born at home as fifth child of eight in Rize. She had no problem of growth and development. Her mother is 67 years old, hausewife and lives with her son and his wife. Her father died from lung cancer 15 years ago. Her mother and father’s marriage is a cross-cousin marriage. She agreed with her father much more than her mother so she was affected by her father’s death greatly. She reported that her mother showed more interest in her male children since her childhood. She finished first school in five years succesfully and went on a religious school. She married five years ago. Her husband is five years older than her, primary school graduate and self-employed. She has two sons at the ages of twelve and seventeen. She was treated because of type 2 diabetes mellitus, obesity and hypertension. It is said that there is a family history of psychotic disorder in the grandfather and grandmother.
Neurological examination and other system examinations, hemogram and biochemical values were evaluated normally.
Mental state examination: She was conscious and fully oriented. There was eye contact. Self care was exaggerated. She was talking with high volume and her mood was euphoric. She was noted to have an anxious affect. Auditory and visual hallucinations were encountered. The reality testing and judgement were impaired. In the thought content there were reference, persecutory and grandiose delusions as well as delusions. Self esteem and explosive behavior had increased.
Clinical course: After aripiprazole treatment upgraded to 30mg/day in the last 4 days obvious changes observed in the style of clothing and behavior of the patient. According to the DSM-IV TR (4) criteria of the manic periods; euphoric mood, grandiosity, increase of self-care and amount of speech, decline in the need of sleep, increase of spending-money and libido and movement were detected. It was reported that there was no depressive symptoms before starting aripiprazole treatment and no mixt episodic symptoms during follow-up period in our clinic in the patient who was presented to the emergency service with an unexpected suicide attempt. Young Mania Rating Scale (YMRS) was evaluated as 31 points. Aripiprazole was reduced gradually and stopped. Haloperidole was added and increased to 10mg/day. In the following period manic symptoms decreased. YMRS dropped to 7 points.
DISCUSSION
In this paper, we presented a case with diagnosis of paranoid schizophrenia that showed manic symptoms after treatment of aripiprazole treatment of 30mg/day. Although similar cases are shown about other antipsychotics’ side effects like this, the case number about aripiprazole is limitted. Acording to a review in which case reports are evaluated between the years 2004-2010, the distribution of 28 cases with atypical antipsychotics induced mania/hypomania is like that; olanzapine-related 7 cases, ketiyapin-related 5 cases, ziprasidone-related 5 cases, aripiprazole treatment-related 4 cases, amisülpirid-induced 2 cases, zotepin induced 2 cases, perospiron-induced 2 cases and paliperido-induced 1 case. It was reported that 24 cases of these are schizophrenia and 4 cases of these are schizoaffective disorder (3). Aripiprazole is an atypical antipsychotic that acts as partial agonist on 5-HT1A and D2 receptors while it acts as antagonist on 5-HT2A receptor. It was reported that there is aripiprazole-induced mania in a patient with cronic schizophrenia who has no mood disorder symptoms before (5). Aripiprazole induced mania has been reported in a male patient with resistant obsessive compulsive disorder in a case report (6). It is not clear that which mecanisms play role on this side effect but it is suggested that partial agonism 5-on HT1A and D2 receptors may lead to an increase in the release of dopamine and may lead to mania (7). Another opinion about this suppors that usage of parsial agonism in patient who takes dopamine antagonist for a long time may increase dopaminergic activity relatively. On the other hand, that is not known exactly how or why dopaminergic hyperactivation triggers hypomania/mania without worsening psychotic symptoms. Antagonism on 5-HT2A reseptor may lead to disappearance of dopaminergic inhibition and mania (5). The mood swings because of antipsychotics use for acute phase and protective treatment of bipolar disorders are noteworthy. Even though the number of reported cases with aripiprazole is rare, we must be careful in terms of these side effects and inform patients and patient relatives about the possible mood symptoms. Further research is needed in terms of which mecanisms are acting on this side effect and determination of risc factors and predictors.
