Abstract
Aripiprazole is an atypical antipsychotic drug chemically characterised as a quinolinone derivate [1]. Aripiprazole is a partial agonist at dopamine D2 and serotonin 5-HT1A− receptors and has antagonist activity at the 5-HT2A receptor. In placebo-controlled studies, aripiprazole treatment was associated with a good safety and tolerability profile, with minimal liability for the sideeffects that limit treatment with other agents, including extrapyramidal side-effects (EPS) [2]. It has been proposed that it may be a useful drug for the treatment of Parkinson's disease-related psychosis without causing a worsening of parkinsonism [3].
EPS reduce the beneficial effects of antipsychotic treatment on the negative, cognitive, and mood symptom domains, while increasing the risk of tardive dyskinesia and reducing compliance. Extensive dopaminergic blockade in the nigrostriatal pathway is the purported mechanism by whichEPS aremanifested [4]. The clinical characteristics suggest that the underlying pathophysiology of druginduced EPS is complex and several putative risk factors have been discussed in the literature. By definition, the atypical antipsychotic agents are significantly better than the conventional agents with regard to EPS. The association of atypical antipsychotic agents with fewer druginduced movement disorders than conventional agents has engendered several pathophysiologic hypotheses [5]. One main hypothesis is that atypical antipsychotics have greater activity in blocking serotonin 5-HT2A receptors than dopamine D2-receptors, which mitigates extrapyramidal symptoms. Here we report the case of a patient who experienced aripiprazole-induced EPS.
A 43-year-old female patient with schizoaffective disorder (meeting the DSM-IV criteria) was admitted to our psychiatric hospital in February 2004. During two comparable previous episodes she was exposed to amisulpride for a few weeks and developed depressive episodes. Blood tests, ECG, EEG and MRI of the brain revealed no abnormal findings. We decided to start an antipsychotic pharmacotherapy with 10 mg aripiprazole daily. The psychotic symptoms remitted partially within the next 2 weeks. On day 18 the aripiprazole dose was increased up to 20 mg daily and side-effects occurred. The patient developed acute orobuccolingual dyskinesias and parkinsonism (rigidity of the extremities). She received 4 mg biperidine daily and the extrapyramidal side-effects remitted quickly. Adose reduction of aripiprazolewas not tolerated regarding the psychotic symptoms. A dose of 20 mg aripiprazole and 4 mg biperidine was continued. The psychotic symptoms disappeared within the next weeks. But the patient developed a depressive episode and 5 mg escitalopram daily was added. The escitalopram dose was increased to 10 mg daily and the depressive symptoms started to disappear.
Atypical antipsychotic agents such as aripiprazole carry a much lower risk of EPS than conventional antipsychotic agents, but the present case shows that druginduced movement disorders still play an important role for clinicians even in patients without putative risk factors. Explaining the underlying mechanisms of antipsychotic drug-induced movement disorders remains a substantial challenge. A number of factors contribute to the difficult task of gaining insight into the pathophysiologic processes of antipsychotic agents and why these agents may lead to drug-induced movement disorders. Further studies are needed with the aim of identifying valid biological markers for EPS susceptibility.