Abstract
To our knowledge, there are no data from epidemiological studies about an association between ventricular ectopics and atypical antipsychotics. Hence a report of this type of cardiac arrhythmia might be of significance as the event occurred during the trial of two medications, which have been recently introduced in Australia – amisulpride and quetiapine [1, 2]. We describe spontaneous and sustained ventricular ectopics of bigeminy and trigeminy types during crossover of amisulpride and quetiapine.
A 67-year-old woman was admitted to a psychogeriatric unit with a relapse of schizoaffective disorder with psychotic symptoms, disorganized behaviour, and irritable mood in the context of noncompliance with clozapine. She had been on clozapine (75–125 mg/daily) in partial remission for more than 18 months. Her psychiatric history included a chronic psychotic illness of more than 30 years duration, multiple admissions to hospital, psychosurgery 30 years previously and trials of numerous antipsychotics. Her medical history comprised hypertension, hypercholesterolaemia, hepatitis at age 29, skull fracture, endometriosis, and severe tardive dyskinesia. She had no history of ischaemic heart disease, heart valve disease, myocarditis, diabetes mellitus or thyrotoxicosis, and she was a non-smoker. Her regular oral medications included clozapine 112.5 mg at night, vitamin E 500 units twice daily and Lipex 10 mg at night. Baseline ECG showed mild sinus tachycardia with QTc of 420 ms.
For the first 3 days she was treated with Clozapine 12.5 mg daily to prevent withdrawal, and after two wash-out days, amisulpride was initiated in the following dose regimen: 50 mg daily for 3 days, 50 mg twice daily for 5 days, and then 50 mg in the morning plus 100 mg at night. On day 14 Epilim was added, initially 200 mg twice daily for 4 days, then 200 mg in the morning plus 500 mg at night. After 3 weeks there had been no significant clinical improvement, and extrapyramidal side-effects emerged in the form of new onset limb tremor and exacerbation of pre-existing tardive dyskinesia. This prompted a switch from amisulpride to quetiapine. Quetiapine was commenced at 50 mg twice daily for 2 days. On day 3 of the crossover, 100 mg of quetiapine was administered and a grossly irregular heart rate was noticed. ECG showed sinus rhythm with ventricular ectopics of trigemy type, ventricular rate 86, intervals PR 176 ms, QTc −404 ms. Blood pressure (BP), body temperature, and oxygen saturation were normal. The patient voiced no physical complaints, and her physical examination was otherwise unremarkable. At the time of the event, her medications included amisulpride 50 mg in the morning plus 100 mg at night, quetiapine 100 mg twice daily, Epilim 200 mg in the morning plus 500 mg at night, Temazepam 10 mg at night, vitamin E 500 units twice daily, Lipex 10 mg at night and Coloxyl 2 tabs at night. Amisulpride was ceased and quetiapine reduced to 50 mg twice daily. Arrhythmia in a form of premature ventricular beats of bigemny and trigemny types continued for five consecutive days. ECG taken on day 3 showed a prolongation of QTc interval up to 465 ms. During this period the patient remained completely asymptomatic and afebrile, BP was stable and on day 6 the ventricular ectopics spontaneously resolved with return to regular sinus rhythm with QTc below 410 ms. Serum electrolytes, EUC, LFT, Ca, Mg, CK, troponin T, C-reactive protein, and FBC, measured on the first day of the episode and 1 week later were all within a normal range, apart from phosphate 1.64 (< 1.43 mmol/L). The level of Epilim was 422 ∝ mol/L. Epilim was discontinued 2 weeks after resolution of ventricular ectopics, and the dose of quetiapine was gradually increased up to 700 mg daily with no recurrence of arrhythmia.
If we assume that the adverse cardiac event did not occur by chance, we can hypothesize that the combination of amisulpride and quetiapine during the crossover might have contributed. The ventricular ectopics occurred when quetiapine in the dose 100 mg daily was added to amisulpride in the dose of 150 mg daily, and spontaneously resolved after discontinuation of amisulpride. The concurrent use of Epilim, the level of which remained within the therapeutic range, is unlikely to have caused the event as the patient continued taking Epilim 2 weeks after the cardiac arrhythmia stopped.
In all available literature, we found only one case report of asymptomatic bradyarrhythmia following administration of amisulpride [3]. Given the extent of worldwide use of atypical antipsychotic agents, it appears that cardiac arrhythmias are a rare complication [4, 5], but we suggest cardiac monitoring is warranted during crossover titration, especially in patients with cardiac malfunction.