Lithium is a good treatment for depression besides being a good treatment for Bipolar Disorder.  It can be used as a sole treatment or as an adjunctive treatment.  In Bipolar Disorder, it is much better than divalproex (Depakote) or carmazepine (Tegretol) at decreasing suicides.  Whether it is better than anti-depressants in preventing suicides in unipolar depression is unknown although anti-depressants do not have a powerful anti-suicidal effect according to double-blind studies.  Like all medications, lithium does cause side-effects.  It causes a modest to moderate weight gain in a fair percentage of patients.  It is inexpensive although blood tests must be done occasionally to assure that the level in not too high or too low.

How Lithium Works: Lithium's actions including its direct inhibitory actions on inositol monophosphatase, inositol polyphosphate 1-phosphatase, glycogen synthase kinase-3, fructose 1,6-bisphosphatase, bisphosphate nucleotidase, and phosphoglucomutase enzymes. Lithium's intracellular downstream targets include adenylate cyclase, the phosphoinositol cascade (and its effect on protein kinase C), arachidonic acid metabolism, and effects on neurotrophic cascades. Molecular effects of lithium. Quiroz JA, Gould TD, Manji HK. NIMH Mol Interv. 2004 Oct;4(5):259-72. Ed: If you understand most of this, your doing better than me.

Lithium Used for Unipolar Depression Long-Term by Harvard: In a prospective open trial report of 55 unipolar depressed patients on lithium for an average of 6.7 years, only 38% needed a second psychiatric medication and only 12% discontinued lithium: 8% side-effects and 4% lack of efficacy.  Days spent in the hospital were markedly reduced from before lithium. Side-effects were modest. Authors were pleased with the results. Effectiveness and outcome predictors of long-term lithium prophylaxis in unipolar major depressive disorder. Baethge C, Gruschka P, Smolka MN, Berghofer A, Bschor T, Muller-Oerlinghausen B, Bauer M. J Psychiatry Neurosci. 2003 Sep;28(5):355-61

Lithium Augmentation for Resistant Depression Helpful: There have been 10 double blind placebo controlled studies of adding lithium to another anti-depressant for the treatment resistant. The majority of randomized controlled trials has demonstrated substantial efficacy of lithium augmentation in partial and non responders to antidepressant treatment. In the placebo-controlled trials, the response rate in the lithium group was 45% and in the placebo group 18% (p<0.001). Berlin. Lithium augmentation therapy in refractory depression-update 2002. Bauer M, Forsthoff A, Baethge C, Adli M, Berghofer A, Dopfmer S, Bschor T. Eur Arch Psychiatry Clin Neurosci. 2003 Jun;253(3):132-9

Desipramine & Lithium Better: In treatment resistant major depression in a PC DB study of desipramine vs. desipramine + lithium, researchers found the combination best especially in the 1^st weeks although by the 4^th week the difference was non-significant. Cappiello, Int Clin Psychopharm 9/98 Yale. More responders to the combination.

Lithium Safer in Pregnancy than Divalproex (Depakote) or Carbamazepine (Tegretol) : Cardiac malformation 1/1000 and may be repaired surgically. Valproic acid and carbamazepine 5% neural tube defects and craniofacial abnormalities and cognitive deficits. Recommends continuing lithium if 4 or more prior episodes or if manic during pregnancy after d/c at start. Ultrasonogram at 20- weeks for cardiac abnormalities. MGH, Psychopharm Bull 98;34:339

No Loss of Bone Mass: Bone mineral densities of 23 patients on lithium with half on lithium for over 3 years and all euthyroid found the densities similar age-matched population norms.

Lithium Augmentation Continuation Better: 29 pt responding to lithium augmentation of anti-depressant DB PC for 4 more months. No relapses with lithium vs. 7/15 with placebo for whom lithium d/c in one week taper after 2-4 weeks of remission. Bauer, Am J Psychiatry 00;157:1429, Berlin Freie U.

Lithium Augmentation Reduced Relapses: 49 >65yos DB PC anti-depressant with or without lithium 0.3-0.7 mEq/L. 2 yr f/u. 8 relapses with placebo vs. 1 with lithium. However, no difference in average MADRS score during f/u. No diff in side-effect. Wilkinson, J Geriatric Psychiatry 02;17:619

Lithium Augmentation of Venlafaxine Possible Benefit: Treatment resistant MDD. 23/60 didn’t respond to venlafaxine 75 TID for 6 weeks. Lithium added and 32% responded over 6 weeks. Hoencamp, J Clin Psychoph 00;20:538

Lithium Augmentation of Clomipramine a Minor Value: A French study of 141 MDD patients were treated with clomipramine with or without lithium in a PC DB 6 week study.  Patients on clomipramine plus lithium improved slightly faster with more patients remitting earlier (15% lower depression scores early in hospitalization reaching significance at 11 days), but at six weeks there was no difference between clomipramine alone vs. the combination.  Multicenter double-blind randomized parallel-group clinical trial of efficacy of the combination clomipramine (150 mg/day) plus lithium carbonate (750 mg/day) versus clomipramine (150 mg/day) plus placebo in the treatment of unipolar major depression. Januel D, Poirier MF, D'alche-Biree F, Dib M, Olie JP. J Affect Disord. 2003 Sep;76(1-3):191-200

Lithium Augmentation Didn’t Help: DB PC of partially responsive patients after 9 months of anti-depressant rx. MGH. Adjunct low dose lithium carbonate in treatment-resistant depression: a placebo-controlled study. Zusky PM, Biederman J, Rosenbaum JF, Manschreck TC, Gross CC, Weilberg JB, Gastfriend DR. J Clin Psychopharmacol 1988 Apr;8(2):120-4

No Benefit in Prepubertal MDD: DB PC 30 pt 6 weeks. J Affect Disord 1998 Nov;51(2):165-75. Says TCAs haven’t been very effective either.

HS Lithium OK; Cuts Suicide in Unipolar: Unipolar depression is a severe recurrent illness with high lifetime morbidity and premature mortality due to suicide. Numerous double-blind, placebo-controlled trials have shown that lithium is very effective at reducing relapses when given as maintenance therapy. It is also very effective when given as maintenance therapy after electroconvulsive therapy. It can be given once a day at night, and controlled trials have shown a 12-hour plasma lithium level between 0.5 and 0.7 mmol/L the most effective, with very slight side effects. Long-term studies of lithium maintenance therapy show a suicide rate of 1.3 suicides per 1000 patient years. Coppen, Surrey, UK, J Clin Psychiatry 2000;61 Suppl 9:52-6

Lithium-Paroxetine Serotonin Syndrome: 17 patients given both with four developing some symptoms of syndrome and two more going manic. J Clin Psychopharm 01;21:474

Lithium Orotate = Carbonate: The orotate salt is available without a prescription over the internet and advertised for depression, The pharmacokinetics of the lithium ion administered as lithium orotate were studied in rats. Parallel studies were carried out with lithium carbonate and lithium chloride. 2 No differences in the uptake, distribution and excretion of the lithium ion were observed between lithium orotate, lithium carbonate and lithium chloride after single intraperitoneal, subcutaneous or intragastric injections (0.5-1.0 mEq lithium/kg) or after administration of the lithium salts for 20 days in the food. 3 The findings oppose the notion that the pharmacokinetics of the lithium ion given as lithium orotate differ from lithium chloride or lithium carbonate. 4 Polyuria and polydipsia developed more slowly in rats given lithium orotate than in those given lithium carbonate or lithium chloride, perhaps due to an effect of the orotate anion. Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats. Smith DF. Br J Pharmacol 1976 Apr;56(4):399-402. Promoted on findserenitynow.com for depression, bipolar, mood swings, migraines, alcoholism, seizures, hepatitis, cirrhosis, and general well-being.