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Drug Interactions between lithium and trazodone

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

lithium traZODone

Applies to: lithium and trazodone

MONITOR CLOSELY: Lithium may enhance the pharmacologic effects of serotonin reuptake inhibitors (e.g., SSRIs, SNRIs, nefazodone, trazodone) and potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. The exact mechanism by which lithium increases serotonergic activity is unknown. The interaction has been reported with selective serotonin reuptake inhibitors including fluoxetine and fluvoxamine and the serotonin-norepinephrine reuptake inhibitor venlafaxine. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: Caution is advised if lithium is prescribed in combination with serotonin reuptake inhibitors. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. The potential risk for serotonin syndrome should be considered even when administering serotonergic agents sequentially, as some agents may demonstrate a prolonged elimination half-life. For example, a 5-week washout period is generally recommended following use of fluoxetine before administering another serotonergic agent. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures.

References

  1. Hadley A, Cason MP "Mania resulting from lithium-fluoxetine combination." Am J Psychiatry 146 (1989): 1637-8
  2. Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13
  3. Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol 10 (1990): 213-7
  4. Noveske FG, Hahn KR, Flynn RJ "Possible toxicity of combined fluoxetine and lithium." Am J Psychiatry 146 (1989): 1515
  5. Muly EC, McDonald W, Steffens D, Book S "Serotonin syndrome produced by a combination of fluoxetine and lithium." Am J Psychiatry 150 (1993): 1565
  6. "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories PROD (2001):
  7. "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company PROD (2001):
  8. Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763
  9. Sobanski T, Bagli M, Laux G, Rao ML "Serotonin syndrome after lithium add-on medication to paroxetine." Pharmacopsychiatry 30 (1997): 106-7
  10. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5
  11. Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6
  12. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  13. "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories (2008):
  14. "Product Information. Savella (milnacipran)." Forest Pharmaceuticals (2009):
  15. Bijl D "The serotonin syndrome." Neth J Med 62 (2004): 309-13
  16. "Product Information. Viibryd (vilazodone)." Trovis Pharmaceuticals LLC (2011):
  17. "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals (2013):
View all 17 references

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Drug and food interactions

Moderate

lithium food

Applies to: lithium

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
View all 4 references

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Moderate

traZODone food

Applies to: trazodone

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
View all 4 references

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Moderate

lithium food

Applies to: lithium

MONITOR: One study has suggested that caffeine withdrawal may significantly increase blood lithium levels. The mechanism may be involve reversal of a caffeine-induced increase in renal lithium excretion.

MANAGEMENT: When caffeine is eliminated from the diet of lithium-treated patients, caution should be exercised. When caffeine consumption is decreased, close observation for evidence of lithium toxicity and worsening of the psychiatric disorder is recommended. Patients should be advised to notify their physician if they experience symptoms of possible lithium toxicity such as drowsiness, dizziness, weakness, ataxia, tremor, vomiting, diarrhea, thirst, blurry vision, tinnitus, or increased urination.

References

  1. Mester R, Toren P, Mizrachi I, Wolmer L, Karni N, Weizman A "Caffeine withdrawal increases lithium blood levels." Biol Psychiatry 37 (1995): 348-50

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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