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
alpha-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.