CPCP: Lithium Neurotoxicity

CPCP Drs Raymond Yu Faisal Tai Alan Schmitt
CPCP Drs Raymond Yu, Faisal Tai, Alan Schmitt

Coming at you with another killer Clinical Problems in Consultation Psychiatry (CPCP), this one on lithium neurotoxicity by the residents currently on the consult service, Drs Raymond Yu, Faisal Tai, and Alan Schmitt, who are working pretty hard this month. They will surely find jobs.

The psychiatry consult service gets called occasionally to help provide safe care for patients who sometimes suffer from lithium neurotoxicity, which can happen for a variety of reasons including dehydration or from drug-drug reactions. An excellent summary of how to manage lithium was written by Dr. James Jefferson, MD, published in Current Psychiatry many years ago.


Another good reference was written by Ivan Netto, MD and Vivek Phutane, MD and published in  The Primary Care Companion for CNS Disorders [1].

We had a very interesting Grand Rounds yesterday too, entitled “A New Picture of Bipolar Disorder Mood States” in which the presenters discussed neuroimaging research they’re doing which tends to implicate the cerebellum as being part of the pathophysiology of manic and depressed states, as well as showing lithium’s salutary effect on both. It reminded me of an Academy of Psychosomatic Medicine (APM) conference a few years ago win which Dr. Jason Caplan, MD, talked about the interface between Neurology and Psychosomatic Medicine. Dr. Caplan mentioned Cerebellar Cognitive Affective Syndrome, which was first described in 1998 by Schmahmann and Sherman [2]. In brief, the syndrome’s affective disturbance can mimic hypomania and can arise from lesions in the cerebellar vermis, which is where the neuroimaging lights up in bipolar disorder, so to speak, according to the Grand Rounds presenters. The affective (and cognitive) dysmetria in Cerebellar Cognitive Affective Syndrome is similar to the undershoot and overshoot cerebellar motor disturbance seen on neurologic exam in patients with cerebellar injury.

One of the challenges in using lithium is the need to communicate effectively with the patient, family, and the primary care physician (PCP). For example, if the PCP prescribes enalapril and is unaware of the potential risk for drug-drug interaction between lithium and this whole class of antihypertensives, then the risk for lithium neurotoxicity is raised. Often enough the psychiatrist and the PCP are not in sync when it comes to collaborative care, which can create unnecessary and dangerous hazards for the patient.

It’ll make psychiatrists think twice before supporting a comeback for lithium in the management of bipolar disorder.


  1. Netto, I. and V. H. Phutane (2012). “Reversible lithium neurotoxicity: review of the literatur.” Prim Care Companion CNS Disord 14(1).
    OBJECTIVE: Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. DATA SOURCES: A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. STUDY SELECTION: A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. DATA EXTRACTION: The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. DATA SYNTHESIS: Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P < .001) and presented mainly with acute organic brain syndrome. In most cases, the therapeutic serum lithium levels were less than or equal to 1.5 mEq/L (P < .001), and dosage regimens were less than 2,000 mg/day. Specific drug combinations with lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. CONCLUSIONS: Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate preventive measures. This recognition will help in early diagnosis and prompt treatment of lithium neurotoxicity.
  2. Schmahmann, J. D. and J. C. Sherman (1998). “The cerebellar cognitive affective syndrome.” Brain 121 ( Pt 4): 561-579.


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