Restless legs syndrome (RLS) is a sensorimotor disorder characterized of an urge to move the legs during periods of rest or inactivity, such as lying or sitting.

Drug-induced RLS, still remains an under- or misdiagnosed condition.

We present a case of a female patient, who received a combination of low dose of quetiapine in addition to venlafaxine and manifested RLS.

Our patient was admitted because of a mixed episode of bipolar II disorder. At admission she was under valproic (1.5gr/QD, plasma levels: 79mg/litre), topiramate (100mg/QD) and venlafaxine (300mg/BID). Quetiapine 150 mg/QD was started at bed time and within 48 hours the patient showed RLS. The physical, neurological and laboratory examination was normal.

The tapering of venlafaxine resulted in the elimination of RLS within 48 hours. After discharge the patient remained in a normothymic state, without RLS, taking valproate 1,5gr/QD, topiramate 100mg/QD and quetiapine 150mg/QD. After 6 months, because of depression, quetiapine was reduced to 100mg/QD and venlafaxine 75mh/QD was added. The previously described RLS symptoms emerged again within 48 hours. This time the tapering of quetiapine and its substitution by olanzapine 10 mg/QD resulted in a prompt and complete elimination of RLS symptoms.

Neither quetiapine alone, nor venlafaxine alone induced RLS to our patient. Clinicians should not overlook the possibility a RLS to be induced by quetiapine-vanlafaxine combination. The removal of one of the two drugs might be beneficial in the RLS's successful treatment.