A case of hypomania with low-dose lamotrigine.

Sir,

Lamotrigine is an effective treatment for acute bipolar depression.[1] Although a recent review concluded that the lamotrigine does not increase the incidence of hypomania or manic switches,[2] cases of lamotrigine-induced manic switches in patients with bipolar disorder have been reported.[34] We would like to report a case of hypomanic switches with low doses of lamotrigine.

A 42-year-old man was referred to our outpatient clinic because of unhappiness and fatigue since more than a year. He had a 19-year history of bipolar disorder that included three psychiatric hospitalizations for manic episodes with psychotic features. His manic episodes were preceded by depressive episodes, which dominated his clinical course. He had been taking lithium 1200 mg/day and olanzapine 2.5 mg/day regularly as a mood stabilizer for more than 2 years. He had previously taken fluoxetine and bupropion for depression, but they were not effective in relieving his depressive symptoms. The patient had complained of weight gain during follow-up; therefore, olanzapine was discontinued. Lamotrigine 25 mg/day was added at bedtime and increased by 25 mg after 2 weeks. However, after 2 weeks, he reported restlessness, decreased need for sleep (5 h/day), improved mood, increased energy, and distractibility. As a result, the dose was reduced to 25 mg/day, which led to amelioration of the hypomanic symptoms. After 2 weeks, his depressive symptoms re-emerged, and he was prescribed lamotrigine 37.5 mg/day. After 1 week, he complained of the same hypomanic symptoms. A diagnosis of hypomania (lamotrigine induced) was made, and the dose was again decreased to 25 mg/day; his symptoms subsequently improved over 2 weeks. He was regularly taking prophylactic lithium during follow-up, and although his blood lithium level was in the therapeutic range (0.89 mEq/L), he experienced lamotrigine-induced hypomania. Lithium 1200 mg/day and lamotrigine 25 mg/day were continued during the follow-up, and he remained stable without the recurrence of hypomania or depression for approximately 1 year.

The temporal correlations between the occurrence of hypomania and increases in lamotrigine doses (37.5 mg and 50 mg) and those between the disappearance of hypomania and decreases in lamotrigine doses (25 mg) suggest that the patient's hypomania was induced by lamotrigine. The mechanism underlying the occurrence of lamotrigine-induced manic switches may be the inhibition of glutamate release, which provides an antidepressant effect.[5] In one case report, the authors suggested that the occurrence of manic switches was related to the titration rate and dosage. In their cases, the manic symptoms manifested after the intake of 200 mg doses or rapid titration.[3] The hypomanic switches that occurred in our case with increasing doses of lamotrigine are in agreement with this previous report. In another recent case report, manic switches occurred after adding lamotrigine to lithium in a small dose (25 mg).[4] We suggest that future case reports should clarify whether lamotrigine plays a role in manic switches. On the other hand, hypomania may be partly due to the course of the underlying illness. This indicates that, in the present case, the remission may not be solely attributed to lithium and lamotrigine, and although the patient has remained stable for approximately 1 year, lithium and lamotrigine may not have a protective effect against future relapses. Therefore, quetiapine can be recommended for bipolar depression in cases such as the present case. Our case suggests the importance of monitoring hypomanic symptoms in bipolar patients treated with lamotrigine.