A placebo-controlled trial of acetyl-L-carnitine and α-lipoic acid in the treatment of bipolar depression.
BACKGROUND
Bipolar disorder may be associated with mitochondrial dysfunction. Therefore, agents that enhance mitochondrial functioning may be efficacious in bipolar disorder. We performed a randomized placebo-controlled trial of the mitochondrial enhancers acetyl-L-carnitine (ALCAR) and α-lipoic acid (ALA) in patients with bipolar depression, and assessed markers of cerebral energy metabolism using phosphorus magnetic resonance spectroscopy.


METHODS
We administered ALCAR (1000-3000 mg daily) plus ALA (600-1800 mg daily) or placebo for 12 weeks to 40 patients with bipolar depression and obtained imaging data at baseline, week 1, and week 12 of treatment in 20 patients using phosphorus 3-dimensional chemical-shift imaging at 4 T. Statistical analysis used random effects mixed models.


RESULTS
We found no significant difference between ALCAR/ALA and placebo on change from baseline in the Montgomery-Asberg Depression Rating Scale in both the longitudinal (mean difference [95% confidence interval], -1.4 [-6.2 to 3.4], P = 0.58) and last-observation-carried-forward (-3.2 [-7.2 to 0.9], P = 0.12) analyses. ALCAR/ALA treatment significantly reduced phosphocreatine levels in the parieto-occipital cortex at week 12 (P = 0.002). Reduction in whole brain total nucleoside triphosphate levels from baseline to week 1 was associated with reduction in Montgomery-Asberg Depression Rating Scale scores (P = 0.02) in patients treated with ALCAR/ALA. However, this was likely a chance finding attributable to multiple statistical comparisons.


CONCLUSIONS
Treatment with ALCAR and ALA at the dose and duration used in this study does not have antidepressant effects in depressed bipolar patients and does not significantly enhance mitochondrial functioning in this patient group.
Biological Psychiatry Laboratory, McLean Hospital, Belmont, MA 02478, USA. bbrennan@partners.org
Brian P
BP
Brennan
John Eric
JE
Jensen
James I
JI
Hudson
Caitlin E
CE
Coit
Ashley
A
Beaulieu
Harrison G
HG
Pope
Perry F
PF
Renshaw
Bruce M
BM
Cohen
D000108:Acetylcarnitine / Q000627:therapeutic use*; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006801:Humans; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D008063:Thioctic Acid / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000928:Antidepressive Agents; D010725:Phosphocreatine; D000108:Acetylcarnitine; D008063:Thioctic Acid