Lithium Induced Neuropathy

Lithium induced neuropathy is a rare side effect of lithium. We will discuss this adverse event in the following sections:

  1. Underlying mechanism.
  2. Clinical Presentation: onset, localization, recovery and prognosis.
  3. Evaluation.
  4. Management.

(1) Underlying Mechanism:

  • intracellular accumulation of lithium and interference with the propagation of action potentials.

(2) Clinical Presentation:


  • Delayed in most cases: 3-7 days.


  • from slight paresis to complete quadriplegia.
  • symmetrical involvement.
  • mostly distal involvement, but proximal limbs can get affected.


  • Recovery can take weeks to months in some cases.
  • Good prognosis: most case reports described a good prognosis with clinical recovery upon discontinuation of lithium.

(3) Evaluation:

(a) Rule out medical causes of neuropathy:

  • Electrolytes: basic metabolic panel (ex: hypernatremia)
  • B12 and folate levels.
  • HbA1c: rule out diabetes as cause of peripheral neuropathy.
  • Urine and serum examination for heavy metal (mercury, lead, copper) levels
  • porphyria (porphyrin studies), if indicated
  • pseudocholinesterase levels, and immune marker, if indicated
  • Cerebrospinal fluid for anti-GQ1b (if indicated to rule out Guillain-Barré syndrome)

(b) Differentiate from lithium toxicity:

  • Check lithium level

Lithium toxicity is associated with:

  • increased muscle tone
  • hyperactive tendon reflexes
  • presence of Babinski sign
  • fasciculations
  • paresthesias
  • note that sensation is normal

Important clinical fact:

  • Brain lithium level is not always accurately reflected in serum lithium level.
  • Cases have documented the worsening of neurological symptoms even after discontinuation of lithium level and with therapeutic or normal lithium levels.

(c) EMG and Nerve Conduction Studies:

  • mostly represents axonal neuropathy.

(4) Management:

(1) Discontinue Lithium level if signs of lithium toxicity.

(2) Evaluate for peripheral neuropathy in every patient on chronic lithium treatment.

(3) If re-challenging with lithium after neuropathy resolution:

  • be mindful of delayed onset and slow resolution of neuropathy side effect.
  • Consider lower dose of lithium with lower therapeutic level, if clinically possible.
  • Switch to another mood stabilizer: positive case of switch to quetiapine.

For Physician’s Guide for Clinical Psychiatry Subscribers:

Course subscribers will have access to the following six chapters discussing the management of both common and rare lithium’s adverse events:

Management of Lithium’s Adverse Events

(1) Lithium and Acute Kidney Injury (Evaluation): read chapter 2.25

(2) Lithium induced Polyuria/polydipsia (nephrogenic diabetes insipidus): read chapter 2.26

(3) Lithium and Risk of Hypercalcemia & Hyperparathyroidism: read chapter 2.27

(4) Lithium induced Tremors: read chapter 2.28

(5) Lithium induced Hypothyroidism: read chapter 2.29

(6) Lithium induced Neuropathy: read chapter 2.30

  • Total chapters= 236 and counting 
  • Chapters and Sections are frequently updated.
  • Each chapter includes references: with either pdf article or pubmed link for each article.
  • Triweekly Email Clinical Summary: subscribers receive 3 emails/week.
  • Goal: is to have all important clinically relevant topics in one course.
  • Annual Subscription of $65/year: for continued access to course on an annual basis.

Dr. Harvinder Singh

Admin, Psychiatry Education Forum

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