Inositol as a treatment for psychiatric disorders: a scientific evaluation of its clinical effectiveness

Townsend Letter for Doctors and Patients, Oct, 2004 by Gina L. Nick

Inositol is a naturally occurring isomer of glucose, though it is generally considered to be a member of the B vitamin family. It is a key intermediate in the intracellular phosphatidyl inositol second messenger pathway activated by numerous serotonergic, cholinergic, and noradrenergic receptors. (1) In this capacity it serves as an important signal transduction molecule, but inositol is also a structural component of cellular membrane phospholipids. (2) Research indicates that inositol is an effective and safe option in the treatment of panic disorder, obsessive-compulsive disorder (OCD), bulimia nervosa, binge eating and/or depression. (3-9) Inositol's efficacy, in the absence of side effects, makes this nutrient an attractive addition to treatment plans for specific mood disorders. Following is a scientific review of inositol for the treatment of mood disorders, including a discussion of its anecdotal use for the treatment of insomnia and its cautioned use by pregnant women for the prevention of neural tube defects and embryopathies.

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Inositol occurs naturally as phytic acid in the fiber component of numerous plant foods, especially whole grains, citrus fruit, nuts, and seeds, and as myoinositol in meat. In the intestinal tract, bacteria break down phytic acid into bioavailable inositol that is easily absorbed via the intestinal epithelium. Myoinositol is found to bioaccumulate most abundantly in the central nervous system, supporting a role for it in neurological function.

Depression

Depressive patients generally have decreased levels of inositol in their cerebrospinal fluid. (3) Researchers now theorize that inositol produces positive clinical results in patients with depression due to intracellular phosphatidyl inositol serving as a second messenger for 5-hydroxytryptamine (5-H[T.sub.2]) receptor signaling mechanisms. Serotonin selective reuptake inhibitors (SSRIs), a family of drugs commonly used to treat depression, have a similar therapeutic profile to inositol in that they inhibit serotonin reuptake in the synaptic cleft. (10)

Levine et al. (4) performed a double-blind, placebo-controlled trial for 28 days on 28 depressed patients using a large dose (12 grams per day) of inositol. The Hamilton Depression (HAMD) Scale was used to evaluate patients after the 28-day trial period, and a significant overall benefit was confirmed in the inositol group compared to the placebo group (Table 1). No changes were noted in liver, kidney, or hematological function as a result of the high-dose inositol supplementation.

Bipolar Depression

Statistically nonsignificant differences favored inositol in 22 subjects treated for 6 weeks for bipolar depression. (11) This study noted the appeal of minimal side effects and the agent's 'natural substance' aspect.

Obsessive-Compulsive Disorder

Levine (3) completed a review of research studies using inositol on psychiatric patients. The review highlighted some interesting findings with OCD patients. Serotonin plays a definitive role in obsessive-compulsive disorder as confirmed by the effectiveness of SSRIs in OCD patients and the fact that serotonin agonists exacerbate the syndrome. Rahman and Neuman (12) effectively reduced serotonin receptor desensitization via the administration of myo-inositol.

These research findings, coupled with the knowledge that SSRIs have proven beneficial in the treatment of OCD, (13) influenced Fux et al. (9) to complete a double-blind, placebo-controlled, random, crossover treatment trial of inositol on OCD. Thirteen patients, all of whom met DSM-III-R criteria for OCD, completed the trial. Six patients began the trial on placebo and seven began the trial on inositol (18 grams per day) for a total of six weeks for the first phase and six weeks for the crossover phase. The researchers administered 18 grams of inositol rather than 12 grams (typical dose for depressive patients) because OCD patients generally respond to higher relative doses of SSRIs than is needed to effect change in most depressives. The OCD patients were free of drug and alcohol abuse and had no evidence of diabetes or GI disorder. OCD was assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and depression and anxiety were assessed using the Hamilton Depression Scale (HDS) and Hamilton Anxiety Scale (HAS). The mean improvement in OCD symptoms from baseline to six weeks was 5.9[+ or -]5.0 for inositol versus 3.5[+ or -]2.8 for placebo (p=0.04; t-test). This indicates a measurable positive response of OCD patients to inositol. Table 2 further details the results of this study with respect to inositol's effect on subscale obsession, subscale compulsion, anxiety, and depression, all of which showed marked improvement with the administration of inositol versus the placebo.

Panic Disorder

Panic attacks are recurring attacks of severe anxiety without an apparent cause. Agoraphobia (irrational fear and avoidance of crowds, travel, and multiple situations), depression, alcohol abuse, and suicide are common symptoms and may be exacerbated by post-traumatic stress. Current treatments usually consist of antidepressant drugs and cognitive-behavioral therapy. (8)