Dyskinesia during Treatment with Duloxetine

Depressive syndromes are common during the course of schizophrenia, with the prevalence of depressive symptoms reaching approximately 35% in patients with schizophrenia [1]. Although in some patients the differentiation between depression and negative syndrome may be difficult, the diagnosis is of pivotal relevance for therapeutic decisions.

With regard to depression in the course of schizophrenia, the limited information available suggests that antidepressants, especially SSRIs [6], reboxetine [7] [8], imipramine [9], and venlafaxine [5], represent effective and safe therapeutic options. Accordingly, treatment guidelines recommend treatment of depressive episodes during the course of schizophrenia with antidepressants [3]. Based on these reports, clinicians may consider the use of selective serotonin and norepinephrine reuptake inhibitors such as duloxetine in the treatment of schizophrenic patients suffering a depressive episode [10].

In the present case, a 30-year-old female patient presented with a lifetime diagnosis of paranoid schizophrenia with at least 3 episodes during the last 16 years, during which time she had been treated with clozapine in varying doses. At the time of inpatient admission, she had been on clozapine monotherapy (150 mg) over the past 12 months. She had never been given mood stabilizers or antidepressants. Upon admission, we noted only mild positive symptoms (PANSS positive scale 14) but relevant negative symptoms (PANSS negative scale 30; SANS 26). A high score (58) in the PANSS general psychopathology scale was mainly due to high scores in guilt, tension, and depression. High scores in the Hamilton Depression Scale (HAMD: 25) and in the Calgary Depression Scale for Schizophrenia (CDSS: 15) supported the assumption of a depressive episode independent of a preexisting negative syndrome. We observed no involuntary movements at admission.

After admission we continued the ongoing long-term clozapine treatment and initiated additional treatment with the triple reuptake inhibitor duloxetine. After 4 days of treatment (final dosage: duloxetine 60 mg), the patient developed considerable involuntary movements, mainly involving the lips, arms, and trunk (Abnormal Involuntary Movement Scale 19) with no parkinsonism (Simpson Angus Scale 5) and only mild akathisia (Barnes Akathisia Scale 8). As the patient's psychopathology showed improvement with regard to the depressive syndrome (HAMD 17; CDSS 9), although not the observed negative symptoms (PANSS negative scale 26; SANS 30), we opted to continue treatment with a lower dose of 30 mg duloxetine. Because dyskinesia continued, we stopped duloxetine treatment after an additional 3 days. During treatment with clozapine monotherapy and, afterwards, combined treatment with clozapine (100 mg) and quetiapine (400 mg), dyskinesia subsided over 4 weeks of treatment (AIMS 0).

The appearance of dyskinesia after adding duloxetine to an ongoing therapy with clozapine, coupled with the complete recovery after stopping the medication, highly suggests that duloxetine, in fact, caused this side effect. Of course, our case does not allow us to draw a definite conclusion on whether duloxetine treatment, combined treatment of duloxetine with clozapine, or an individual predisposition contributed to the involuntary movements. However, in this patient clozapine treatment was initiated due to non-response to typical antipsychotics and not due to dyskinesia or other untoward effects of these drugs. Thus, one may hypothesize that duloxetine, similar to SSRIs [2] [4], may induce dyskinesia in vulnerable subjects. To the best of our knowledge this is the first report discussing dyskinesia following administration of duloxetine and may thus contribute to an increased awareness with regard to extrapyramidal symptoms during treatment with selective serotonin and norepinephrine reuptake inhibitors.

References

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