title: A preliminary investigation of alpha-lipoic acid treatment of antipsychotic drug-induced weight gain in patients with schizophrenia.
abstract: 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.
authors.affiliation: Department of Psychiatry and Institute of Behavioral Science in Medicine, College of Medicine, Yonsei University, Seoul, Republic of Korea.
authors.forename: Eosu
authors.initials: E
authors.lastname: Kim
authors.forename: Dong-Wha
authors.initials: DW
authors.lastname: Park
authors.forename: Song-Hee
authors.initials: SH
authors.lastname: Choi
authors.forename: Jae-Jin
authors.initials: JJ
authors.lastname: Kim
authors.forename: Hyun-Sang
authors.initials: HS
authors.lastname: Cho
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001066:Appetite / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D010054:Brief Psychiatric Rating Scale / Q000706:statistics & numerical data; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003863:Depression / Q000139:chemically induced; D005215:Fasting / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D012008:Recurrence; D012559:Schizophrenia / Q000188:drug therapy*; D008063:Thioctic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000975:Antioxidants; D014150:Antipsychotic Agents; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D008063:Thioctic Acid