Weight gain and other metabolic disturbances have now become discouraging, major side effects of atypical antipsychotic drugs (AAPDs). The novel strategies required to counteract these serious consequences, however, should avoid modulating the activities of the neurotransmitter receptors involved because those receptors are the therapeutic targets of AAPDs. Adenosine monophosphate-activated protein kinase is an enzyme that plays a pivotal role in energy homeostasis. We hypothesized that α-lipoic acid (ALA), which is known to modulate adenosine monophosphate-activated protein kinase activity in the hypothalamus and peripheral tissues, would ameliorate AAPD-induced weight gain.
We describe the case series of a 12-week ALA trial in schizophrenia patients treated with AAPDs. Two of 7 enrolled subjects were dropped from the study because of noncompliance and demand for new medication to treat depressive symptoms, respectively.
The mean (SD) weight loss was 3.16 (3.20) kg (P = 0.043, last observation carried forward; median, 3.03 kg; range, 0-8.85 kg). On average, body mass index showed a significant reduction (P = 0.028) over the 12 weeks. During the same period, a statistically significant reduction was also observed in total cholesterol levels (P = 0.042), and there was a weak trend toward the reduction in insulin resistance (homeostasis model assessment of insulin resistance) (P = 0.080). Three subjects reported increased energy subjectively. The total scores on the Brief Psychiatric Rating Scale and the Montgomery-Asberg Depression Rating Scale did not vary significantly during the study.
These preliminary data suggest the possibility that ALA can ameliorate the adverse metabolic effects induced by AAPDs. To confirm the benefits of ALA, more extended study is warranted.
Department of Psychiatry and Institute of Behavioral Science in Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea; and Severance Mental Health Hospital, Gyeonggi-do, Republic of Korea.
Received June 26, 2007; accepted after revision December 20, 2007.
This study was supported by a grant from the Institute of Behavioral Science in Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea. α-lipoic acid was generously provided by ILDONG Pharmaceutical Co., Ltd., Seoul, Republic of Korea.
Address correspondence and reprint requests to Hyun-Sang Cho, MD, Department of Psychiatry and Institute of Behavioral Science in Medicine, Severance Mental Health Hospital, 696-6 Tanbeol-dong, Gwangju-si, Gyeonggi-do 464-100, Republic of Korea. E-mail: firstname.lastname@example.org.