Lithium response

Del Zompo, M., Ardau, R., Palmas, M. A. etal. (1999). Lithium response association study with two candidate genes. Mol. Psychiatry, 4(1), S66-S67. 

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

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. 

Blackburn C, Bai M, LeCompte KA et al (1994) Lithium responsive fluorophores derived from monoaza-12-crown-4 and coumarin. The influence of a methoxy side-arm on photophysical properties. Tetrahedron Lett 43 7915-7918... 

Bipolar depression Rapid cycling Poor lithium response Secondary mania Rapid cycling Poor lithium response... 

There are no randomized, double-blind, controlled studies of hospitalized children and adolescents with acute mania. Two systematic, albeit open, studies of lithium in hospitalized, acutely manic adolescents had response rates of 67%-80% in classic manic adolescents, and 33%-40% in manic adolescents with prior ADHD (Strober et al., 1988 1998). In a discontinuation study in which manic adolescents stabilized on lithium were subsequently assigned double-blind to placebo or continuation treatment, the response rate was 53.5%, and the presence of prior ADHD made no difference in outcome (Kafantaris et al., 1998). However, the presence of psychosis decreased the likelihood of lithium response and antipsychotic medication was necessary for stabilization. Naturalistic discontinuation of lithium (because of noncompliance) after stabilization resulted in relapse rates of 90% vs. 37.5% for those remaining on lithium (Strober et al., 1990). A NIMH multisite study is currently examining this issue more systematically. 

Duffy, A., Alda, M., Kutcher, S., Fusee, C., and Grof, P. (1998) Psychiatric symptoms and syndromes among adolescent children of parents with lithium-responsive or lithium-nonresponsive bipolar disorder. Am Psychiatry 155 431 33. 

Although studies reviewed thus far support the efficacy of lithium treatment for acute mania, the presence of concurrent depression or depressive symptoms during mania, the so-called mixed state, has been associated with poor lithium response. In 1976, Himmelhoch et al. observed that patients with mixed states were significantly less likely to demonstrate a good treatment response than were manic patients [42% vs. 81%] in a retrospective chart review of 84 consecutively referred patients with bipolar disorder. Secunda et al. [1985] reported on 18 patients with mania studied as part of the Collaborative Study of the Psychobiology of Depression and found that patients with concomitant depression and mania [n = 8] had a significantly lower rate of... 

Other factors associated with poor lithium response in mania include a history of prior lithium failure and a diagnosis of schizoaffective disorder. Bowden et al. [1994b] observed in a double-blind, placebo-controlled trial of patients with acute mania that those with a history of lithium response improved on lithium in this trial, whereas those with a history of prior lithium failure did not. Patients with a diagnosis of schizoaffective disorder may respond less well to lithium than patients with bipolar disorder, although this has not been extensively studied [Keck et al. 1994, for review]. 

Bowden et al. [1994b] observed that a history of lithium nonresponse predicted lithium nonresponse, but not valproate nonresponse. Taken together, these studies suggest that a history of lithium nonresponse does not predict valproate nonresponse. Notably, no studies have examined whether a history of valproate treatment failure predicts future valproate or lithium response. 

This group investigated patients presenting with acute schizophrenic symptoms who underwent a drug-free washout period, received lithium only initially, and then antipsychotics later (374). Lithium was ineffective for classic schizophrenia, but some patients who met criteria for schizophreniform disorder did respond to lithium. Whether schizophreniform illness is a variant of mood disorders (a reasonable hypothesis in view of their lithium response) or a separate entity that is lithium-sensitive is still unclear. It is known that these patients have family histories that include mood-disordered as well as schizophrenic relatives. In a small pilot study, physostigmine (a drug with possible antimanic but no antipsychotic properties) benefited schizophreniform patients who responded to lithium, but had no effect in those who did not (Carver DL, personal communication). 

Hirschowitz J, Casper R, Garver DL, et al. Lithium response in good prognosis schizophrenia. Am J Psychiatry 1980 137 916-920. 

In summary, there is evidence for a higher relapse rate in patients not maintained on adequate levels of lithium, the potential for concurrent drugs (e.g., antidepressants) to exacerbate the disorder, a more rapid recurrence with abrupt discontinuation, and possible compromised future lithium responsiveness when it is stopped (43, 162).Compliance issues remain a major factor in providing adequate long-term treatment. 

Prien RF, Caffey EM Jr, Klett CJ. Factors associated with lithium responses in the prophylactic treatment of bipolar manic-depressive illness. Arch Gen Psychiatry 1974 31 189-192. 

When a patient responds to lithium, the inevitable question of duration of therapy arises. The period of highest risk for relapse is at least the first 6 months after remission, but this vulnerable interval may extend up to 18 months (207). Therefore, many clinicians recommend leaving the lithium-responsive patient on medication for at least 2 years after remission. 

Wagemaker, H., Lippman, S., 8c Bryant, D. R. (1979, November/December). Lithium response of a patient diagnosed as a paranoid schizophrenic. Psychiatric Opinion, p. 45. 

Rybakowski JK, Suwalska A, Skibinska M, Szczepankiewicz A, Leszczniska-Rodziewicz A, Permoda A, Czerski PM, Hauser J. Prophylactic lithium response and polymorphism of the brain-derived neurotrophic factor gene. Pharmacopsychiatry 2005 38 166-70. 

Rosenthal, J., A. Strauss, L. Minkoff, and A. Winston. 1986. Identifying lithium-responsive bipolar depressed patients using nuclear magnetic resonance. American Journal of Psychiatry 143 779-80. 

These findings have important implications for the treatment of bipolar affective disorder. Some agents used to treat partial-complex seizures such as carbamazepine and various valproate formulations have been found to be effective in bipolar affective disorder (Bowden 1995). One such agent, divalproex, is now the most commonly prescribed antimanic agent. These agents may be more effective in subtypes of mania that are not lithium responsive. As noted earlier, African Americans are more often prescribed antipsychotics. Poor tolerance of lithium maybe a factor. Improving access to alternatives to lithium may reduce the need for antipsychotics in some African Americans with mania. 

Lenox RH, Wang L. Molecular basis of lithium action integration of lithium-responsive signaling and gene expression networks. Mol Psychiatry 2003 8 135-144. 

Backlund L, Ehnvall A, Hetta J, Isacsson G, Angstromgen H. Identifying predictors for good lithium response—a retrospective analysis of 100 patients with bipolar disorder using a life-charting method. Eur Psychiatry 2009 24(3) 171-7. 

Stochino ME, Deidda A, Asuni C, Cherchi A, Manchia M, Del Zompo M. Evaluation of lithium response in episodic cluster headache a retrospective case series. Headache 2012 52(7) 1171-5. 

In addition to schizophrenia there ar a variety of other episodic or periodic psychopathological states for which lithium responsiveness has been claimed. These have been reviewed by Kline and Simpson and Gerbino et al. and include some cases of epilepsy, unstable character disorder, periodic catatonia, cycloid psychosis, and episodic alcoholism associated wdth de-pression. ... 

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