LITHIUM

Lithium is a tried and tested medication, efficacious in acute mania, prophylaxis of classical bipolar disorder (Groff et al, 1993) and when the disorder has a mania/hypomania-depression-euthymia course (Faedda et al, 1991). Although systematic studies have not been conducted or reported, analysis of data and clinical experience suggest that Lithium is likely less effective in rapid cycling, mixed states, with comorbid substance abuse and in secondary bipolar disorder (Calabrese et al, 1996). It has proven, significant antidepressant properties when compared with Divalproex and Carbamazepine.

Lithium has a narrow therapeutic range between 0.8 and 1.1 mmols/l. Above this there is markedly increased risk of adverse events and toxicity, while below this there is increased risk of relapse. At levels of 0.4-0.6 mmols/1 the risk of relapse is increased by more than 2.5 times (Gelenberg et al, 1989). The onset of action is usually between 7-10 days. Acute adverse effects can create non-adherence in 30-50% of cases and there is the significant long-term risk of hypothyroidism, which is treatable. The teratogenic risk, of Ebstein’s cardiac anomaly, is present but much lower than previously thought (Cohen, 1992). The teratogenic risk is likely lower than that posed by Divalproex and Carbamazepine.

References
Calabrese JR, Fatemi SH, Kujawa M, Woyshville MJ. 1996. Predictors of Response to Mood Stabilizers. J Clin Psychopharmacology. 16. 2. Suppl 1 24S-30S.

Cohen LS. 1992. The Use of Psychotropic Drugs during Pregnancy and Puerperium. Currents in Affective Illness. Vol XI: 9. 5-13.

Faedda GL, Baldessarini RJ, Tohe M, Strakowski SM, Waternaux C. Episode Sequence in Bipolar Disorder and Response to Lithium Treatment. 1991. Am J Psychiatry. 148. 1237-1239.

Gelenberg AJ, Kane JN, Keller MB. 1989. Comparison of Standard and Low Serum Levels of Lithium for Maintenance Treatment of Bipolar Disorders. N Engl J Med. 321: 1489-1493.

Grof P, Alda M. Grof E, Fox D, Cameron P. 1993. The Challenge of Predicting Response to Stabilizing Lithium Treatment: the Importance of Patient Selection. Br J Psychiatry. 163: 16-19.

Predictors of Lithium Response

Previous good response to Lithium, positive family history of bipolar disorder and response to Lithium, pure but not severe mania, classical bipolar disorder with an episode sequence of mania-depression-euthymia and adequate serum Lithium levels are all associated with good response to Lithium (Faedda et al, 1991; Gelenberg et al, 1989; Groff et al, 1993).

Faedda GL, Baldessarini RJ, Tohe M, Strakowski SM, Waternaux C. Episode Sequence in Bipolar Disorder and Response to Lithium Treatment. 1991. Am J Psychiatry. 148. 1237-1239.

Gelenberg AJ, Kane JN, Keller MB. 1989. Comparison of Standard and Low Serum Levels of Lithium for Maintenance Treatment of Bipolar Disorders. N Engl J Med. 321: 1489-1493.

Grof P, Alda M. Grof E, Fox D, Cameron P. 1993. The Challenge of Predicting Response to Stabilizing Lithium Treatment: the Importance of Patient Selection. Br J Psychiatry. 163: 16-19.

Predictors of Lithium Failure

Multiple previous episodes, rapid cycling and mixed states, significant comorbidity with alcohol or substances and personality disorder and serum levels below 0.6 mmols/l are all predictive of failure to respond to Lithium (Calabrese et al, 1996).

References
Calabrese JR, Fatemi SH, Kujawa M, Woyshville MJ. 1996. Predictors of Response to Mood Stabilizers. J Clin Psychopharmacology. 16. 2. Suppl 1 24S-30S

Lithium: Adverse Effects and Interactions

The high frequency of non-adherence to Lithium treatment (30-50%) is often associated with adverse effects, particularly in the early stages of treatment. Cognitive impairment, tremor, acne polyuria and polydipsia, muscle weakness and weight gain can be associated with non-compliance, particularly in adolescents, young adults and the elderly. (Gitlin et al, 1984). Long term adverse effects on thyroid functioning and the kidneys, especially in patients with a previous or family history of renal problems, suggest the value of caution and usefulness of regular monitoring. Lithium has teratogenic potential, albeit posing less risk than previously stated for Ebstein’s cardiac anomaly. Lithium has a narrow therapeutic range and toxicity can be induced by changed in electrolyte and fluid balance. Lithium can be lethal in overdose.

Many medications interact adversely with Lithium. Commonly, this results from alterations in serum concentrations of either Lithium or the concomitant medications. Potential for neurotoxicity with Carbamazepine, decreased serum Lithium levels with calcium channel blocks and xanthines, and increased serum levels with most psychotropics, thiazides and ACE inhibitors should be borne in mind. Patients should be informed about these potential interactions in advance, and screened closely for the use of other medications, including over the counter medications, when side effects appear.

References
Gitlin MJ, Jamison KR. 1984. Lithium Clinics: Theory and Practice. Hospi Comm Psychiatry. 35: 363-368.

Effects of Abrupt Discontinuation of Lithium

Lithium should only be discontinued gradually when it has been used successfully for prophylaxis in bipolar disorder. This discontinuation should be achieved over 2-3 months, and not before 4 weeks if possible. Abrupt or rapid discontinuation (less than 2 weeks) is associated with significantly higher relapse rates not only in the first few months but also over 3-5 years (Baldessarini et al, 1996). It is reasonable, at this stage, to extrapolate these findings and caution against the abrupt discontinuation of any mood stabilizer treatment.

References
Baldessarini RJ, Tondo L, Faedda GL, Suppes TR, Floris G, Rudas N. 1996. Effects of the Rate of Discontinuing Lithium Maintenance Treatment in Bipolar Disorders. J Clin Psychiatry. 57:10. 441-448.