Lithium affective disorders

Lithium is commonly used for bipolar affective disorders. Lithium however has a narrow therapeutic index and high risk for toxicity (Groleau 1994). The use of loop diuretics or ACE-inhibitors significantly increases the risk of hospitalisation for lithium toxicity in the elderly (Juurlink et al. 2004). Treatment of elderly patients with lithium should be thoroughly monitored. 

In a review of five randomized controlled trials of prevention of relapse in 770 patients with bipolar affective disorder, lithium has been compared with placebo (98). Lithium was more effective than placebo in preventing all relapses and manic relapses, but the effect on depressive relapses was not as impressive and was termed equivocal by the authors. This is not particularly new information, although several of the studies that were included in this meta-analysis were more recent and the analysis was presented as odds ratios rather than episode frequency. 

Manic depression currently affects up to 2 percent of the world s population. Clinical studies demonstrate proven effectiveness of lithimn treatment for bipolar affective disorder. Lithium is taken orally and has been used successftdly by some patients for periods exceeding a decade. The action is prophylactic, meaning that it is able to prevent the occurrence of the manic and depressive mood swing phases of the disease once the patient has been... 

The molten carbonate fuel ceU uses eutectic blends of Hthium and potassium carbonates as the electrolyte. A special grade of Hthium carbonate is used in treatment of affective mental (mood) disorders, including clinical depression and bipolar disorders. Lithium has also been evaluated in treatment of schizophrenia, schizoaffective disorders, alcoholism, and periodic aggressive behavior (56). 

Cookson JC, Sachs GS (1999). Lithium clinical use in mania and prophylaxis of affective disorders. In Buckley PF, Waddington JL, eds, Schizophrenia and Mood Disorders The New Drug Therapies in Clinical Practice. Oxford Butterworth Heinemann. 

The evidence base for clinical decisions based on cost-effectiveness for the affective disorders is less clear than for schizophrenia. In bipolar disorder the primary effectiveness of the mainstay treatments, lithium and anticonvulsant pharmacotherapy, is undergoing considerable revision (Bowden et al, 2000). Until this is clarified, cost-effectiveness studies are probably premature. Nevertheless the cost burden in bipolar disorder is qualitatively similar to that in schizophrenia, with in-patient costs being the primary burden and associated social costs in treated patients. The drug costs are even less than those for schizophrenia. In Chapter 5 John Cookson suggests there is little economic evidence to drive prescribing decisions. The in-patient burden does not seem to have altered with the introduction of lithium. The only drug-related study (Keck et al, 1996) showed an obvious difference in treatment costs only when lithium was compared with sodium valproate. Since these are both cheap drugs this is unlikely to influence clinical decisions. The main question is what impact... 

Depression and mania are both affective disorders but their symptoms and treatments are quite distinct. Mania is expressed as heightened mood, exaggerated sense of self-worth, irritability, aggression, delusions and hallucinations. In stark contrast, the most obvious disturbance in depression is melancholia that often co-exists with behavioural and somatic changes (Table 20.1). Some individuals experience dramatic mood swings between depression and mania. This is known as "bipolar disorder which, like mania itself, is treated with lithium salts or neuroleptics. 

Lithium is therapeutically used in the prevention of major changes in mood which are characteristic of the affective disorders (Birch et al. 1994). The therapy can be... 

Grof, P., Alda, M., Grof, E., Zvolsky, P. Walsh, M. (1994). Lithium response and genetics of affective disorders. /. Affect. Disord., 32, 85-95. 

The extensive clinical experience with these drugs in epilepsy shows they are better tolerated and less toxic than lithium (Bowden and Muller-Oerlinghausen, 2000 Rang et ah, 2003). Since the dose regimens for epilepsy and affective disorders are similar, it would be expected that the levels of adverse drug reactions would also be similar. With... 

Alda M, Grof P, Grof E, Zvolsky P, Walsh M. Mode of inheritance in families of patients with lithium-responsive affective disorders. Acta Psychiatr Scand 1994 90[4] 304—310. 

Zis AP, Grof P, Goodwin FK. The Natural Course of Affective Disorders Implications for Lithium Prophylaxis. Amsterdam Excerpta Medica 1979, 391-398. 

Lazarus, J. H., McGregor, A. M., Ludgate, M. et al. Effect of lithium carbonate therapy on thyroid immune status in manic depressive patients a prospective study. /. Affect. Disord. 11 155-160,1986. 

Gardner, R., and Mages, R., Prophylactic lithium in affective disorders. iMHCct ii, 275-279 (1971). 

Pharmacology Lithium alters sodium transport in nerve and muscle cells, and effects a shift toward intraneuronal catecholamine metabolism. The specific mechanism in mania is unknown, but it affects neurotransmitters associated with affective disorders. Its antimanic effects may be the result of increases in norepinephrine reuptake and increased serotonin receptor sensitivity. Pharmacokinetics ... 

Geriatric Considerations - Summary Volume of distribution (Vd), clearance, and half-life are significantly altered in older adults. Lithium toxicity may occur within the usual adult therapeutic range. Older adults are likely to exhibit toxic effects at lower serum concentrations. Significantly lower doses are often efficacious for affective disorders than are used in younger adults. Monitor serum concentrations closely, increased riskof lithium toxicity when a diuretic, NSAID, or ACE Inhibitor is started in a patient already taking lithium. 

Geller, B., Cooper, T.B., Zimerman, B., Frazier, J., Williams, M., Heath, J., and Warner, K. (1998) Lithium for prepubertal depressed children with family history predictors of future bipolarity a double-blind, placebo-controlled study. / Affect Disord, 51 165-175. 

Are childhood psychiatric histories of bipolar adolescents associated with family history, psychosis, and response to lithium treatment / Affect Disord 51 153-164. 

Strober, M., DeAntonio, M., Schmidt-Lackner, S., Freeman, R., Lam-pert, C., and Diamond,/. (1998) Early childhood attention deficit hyperactivity disorder predicts poorer response to acute lithium therapy in adolescent mania. / Affect Disord 51 145-151. 

Rivinus, T.M. and Harmatz, J.S. (1979) Diagnosis and lithium treatment of affective disorders in the retarded five case studies. Am Psychiatry 136 551-544. 

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Coppen A, Peet M, Bailey J, et al Double-blind and open prospective studies of lithium prophylaxis in affective disorders. Psychiatiia, Neurologia, Neurochirurgia 76 500-510, 1973... 

Coppen A, Ghose K, Montgomery S, et al Continuation therapy with amitriptyline in depression. Br J Psychiatry 133 28-33, 1978 Coppen A, Swade C, Wood K Lithium restores abnormal platelet 5-HT transport in patients with affective disorders. Br J Psychiatry 136 235-238, 1980 Coppen A, Swade C, Jones SA, et al Depression and tetrahydrobiopterin the folate connection. J Affect Disord 16 103-107, 1989 Cordell B 3-Amyloid formation as a potential therapeutic target for Alzheimer s disease. Annu Rev Pharmacol Toxicol 34 69-89, 1994 Corkin S Acetylcholine, aging, and Alzheimer s disease imphcations of treatment. Trends Neurosci 4 287-290, 1981... 

Coxhead N, Silverstone T, Cookson J Carbamazepine versus lithium in the prophylaxis of bipolar affective disorder. Acta Psychiatr Scand 85 114-118, 1992... 

Cummings JL, Miller B, Hill MA, et al Neuropsychiatric aspects of multi-infarct dementia and dementia of the Alzheimer type. Arch Neurol 44 389-393, 1987 Cundall RL, Brooks PW, Murray LG A controlled evaluation of lithium prophylaxis in affective disorders. Psychol Med 2 308-311, 1972 Cutler NR, Haxy J, Kay AD, et al Evaluation of zimeldine in Alzheimer s disease cognitive and biochemical measures. Arch Neurol 42 744-748, 1985 Czyrak A The effect of chronic nifedipine and ECS in the forced swimming test in rats. PolJ Pharmacol 45 191-195, 1993... 

Dunner DL, Stallone FL, Fieve RR Lithium carbonate and affective disorders, V a double-blind study of prophylaxis of depression in bipolar illness. Arch Gen Psychiatry 33 117-120, 1976... 

Fieve RR, Platman SR, Plutchik RR The use of lithium in affective disorders, I acute endogenous depression. Am J Psychiatry 125 79-83, 1968 Fieve RR, Kumbaraci T, Dunner DL Lithium prophylaxis of depression in bipolar I, bipolar II, and unipolar patients. Am J Psychiatry 133 925-930, 1976 File SE Rapid development of tolerance to the sedative effects of lorazepam and triazolam in rats. Psychopharmacology 73 240-245, 1981... 

Garcia-Sevilla JA, Guimon J, Garcia-Vallejo P, et al Biochemical and functional evidence of supersensitive platelet alpha-2-adrenoceptors in major affective disorder effect of long-term lithium carbonate treatment. Arch Gen Psychiatry 43 51-57, 1986... 

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