Permanent Pacing-Aid to Carry Out Long-term Lithium Therapy in Manic Patient With Symptomatic Bradycardia

Lithium is commonly used to treat and prevent affective disorders. Lithium may cause cardiovascular adverse events such as arrhythmia, hypotension and electrocardiographic (ECG) T-wave changes [1]. In rare cases, lithium may cause bradycardia, which usually subsides after drug discontinuation [3]. In this paper, we report a case in which lithium induced repeatedly sinus node dysfunction. Due to intolerance against other mood stabilisers, lithium treatment was carried out under permanent pacing.

The patient was a 65-year-old man with first episode of manic disorder. He received sotaloli drops for glaucoma and atenololi for essential hypertension. He started lithium treatment for manic symptoms, and remained asymtomatic for two years. Lithium blood levels laid between 0.5 and 0.7 mmol/l. After that, he exhibited sinus bradycardia ad 30 beats per min. Atenololi and sotaloli were stopped, but the bradycardia persisted. Atropine increased the heart rate to normal level. Lithium was also withdrawn and bradycardia subsided. Within two weeks, the patient underwent a manic episode and was hospitalised. He could not tolerate thioridazine and valproate. Carbamazepine was not effective against his manic symptoms. Lithium was started again, but the patient promptly showed bradycardia. The patient underwent specialised cardiac evaluation, and a pacemaker was installed. After that lithium was reintroduced. The patient's manic symptoms subsided, and the cardiac pacemaker functioned well. At the therapeutic lithium levels, the patient was asymptomatic and functioned well socially until his death of lung cancer after three years.

The patient developed bradycardia after 2 years of lithium treatment. Bradycardia persisted despite discontinuation of beta-adrenoreceptor blocking agents. When the lithium was stopped, bradycardia promptly subsided and started again when lithium was restarted. These findings strongly suggest that reversible sinus node dysfunction in this patient was induced by lithium. The patient was unable to tolerate or did not respond to other mood-stabilising therapies. So, restarting lithium therapy was considered under permanent pacing. To our knowledge, this is the first case where lithium maintenance therapy was successfully carried out in a manic patient under permanent pacing.

Sinus node dysfunction due lithium therapy is not common side effect. Josep and Vieweg reviewed 16 cases of sinus node dysfunction induced by therapeutic levels of lithium [2]. Of 12 cases in which lithium was discontinued, 10 cases recovered to normal sinus rhythm, whereas two did not; in one case, sick sinus syndrome persisted, and in the other, intermittent sinoatrial block and atrioventricular conduction problems persisted. In our patient, sinus node dysfunction may be connected with underlying heart disease. Ageing is known to be decrease the number of cells in the sinus node [4]. The mechanism of lithium induced bradycardia is not clear. In our patient, atropine rapidly returned normal rhythm. This may suggest that the parasympathic nervous system plays a role in bradycardia. Nevertheless, Rosenqvist et al. did not find changes in the function of the parasympathic nervous system in connection with lithium-induced bradycardia [3].

In conclusion, lithium may sometimes cause clinically significant bradycardia. However, this side-effect is rare, but careful follow-up is required, especially in elderly patients treated with lithium. When long-term lithium therapy is necessary in patients with bradycardia, cardiac pacing can maintain sinus rhythm to carry out maintenance treatment.

References

• 1 Brady H R, Horgan J H. Lithium and heart: Unanswered questions.  Chest. 1988;  93 166-169
• 2 Josep M, Vieweg V. Eletrocardiographic changes of sinus bradycardia and sinus node dysfunction among patients with therapeutic levels of lithium.  Depression. 1994/1995;  2 226-231
• 3 Rosenquist M, Bergfeldt L, Aili H, Mathe A A. Sinus node dysfunction during long-term lithium treatment.  British Heart Journal. 1993;  70 371-375
• 4 Wei J Y. Age and the cardiovascular system.  N. Engl. J. Med.. 1992;  327 1735-1739