Inositol as an add-on treatment for bipolar depression.
OBJECTIVE
Inositol is a constituent of the intracellular phosphatidyl inositol (PI) second messenger system, which is linked to various neurotransmitter receptors. Inositol crosses the blood-brain barrier in pharmacological doses, and has shown efficacy in a small double-blind study of unipolar depression. This pilot study evaluated its potential efficacy and safety in bipolar depression.


METHODS
Twenty-four consenting adult men and women with DSM-IV bipolar depression (bipolar I = 21; bipolar II = 3) were randomly assigned to receive either 12 g of inositol or D-glucose as placebo for 6 weeks. Efficacy and safety ratings were done weekly. Thymoleptic medications (lithium, valproate, carbamazepine) in stable doses and at therapeutic levels at study entry were continued unchanged.


RESULTS
Two subjects receiving placebo dropped out early due to worsening or non-adherence to the protocol. Among the 22 subjects who completed the trial, six (50%) of the inositol-treated subjects responded with a 50% or greater decrease in the baseline Hamilton Depression Rating Scale (HAM-D) score and a Clinical Global Improvement (CGI) scale score change of 'much' or 'very much' improved, as compared to three (30%) subjects assigned to placebo, a statistically nonsignificant difference. On the Montgomery-Asberg Depression Rating Scale (MADRS), eight (67%) of twelve inositol-treated subjects had a 50% or greater decrease in the baseline MADRS scores compared to four (33%) of twelve subjects assigned to placebo (p = 0.10). Inositol was well tolerated with minimal side effects, and thymoleptic blood levels were unaltered.


CONCLUSIONS
These pilot data suggest a controlled study with an adequate sample size, and the appropriate rating scale may demonstrate efficacy for inositol in bipolar depression. The tolerability and the 'natural substance' aspect of inositol may be particularly appealing to subjects with bipolar depression.
Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, PA, USA. chengappakn@msx.upmc.edu
K N
KN
Chengappa
J
J
Levine
S
S
Gershon
A G
AG
Mallinger
A
A
Hardan
A
A
Vagnucci
B
B
Pollock
J
J
Luther
J
J
Buttenfield
S
S
Verfaille
D J
DJ
Kupfer
D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D001812:Blood-Brain Barrier / Q000187:drug effects; D002220:Carbamazepine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007294:Inositol / Q000494:pharmacology / Q000627:therapeutic use*; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use
D000927:Anticonvulsants; D018692:Antimanic Agents; D002220:Carbamazepine; D007294:Inositol; D014635:Valproic Acid; D008094:Lithium