Lithium with Yohimbine Interaction Details
Brand Names Associated with Lithium
- Eskalith®
- Eskalith® CR
- Lithium
- Lithobid®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 21, 2023
Interaction Effect
Increased risk of manic episodes
Interaction Summary
Yohimbine may exacerbate bipolar disorder by precipitating manic episodes. This effect has been noted in 3 case reports, generally within one to two hours of yohimbine administration. The authors concluded that patients with a bipolar diathesis are predisposed to the psychogenic effect of yohimbine. Yohimbine appears to block inhibitory alpha2-adrenergic receptors on sympathetic nerve endings, increasing noradrenergic output through negative feedback. Alpha2-adrenoceptors may be involved in the pathogenesis of psychiatric disorders . Theoretically, patients taking lithium for bipolar disorder may experience a return of manic symptoms if they take yohimbine.
Severity
Moderate
Onset
Rapid
Evidence
Probable
How To Manage Interaction
Avoid concomitant use of yohimbine and lithium.
Mechanism Of Interaction
Increased norepinephrine release by yohimbine
Literature Reports
A) Yohimbine challenges were administered to 55 patients with major depression, 39 patients with agoraphobia and panic disorder, and 20 normal control subjects. Three patients developed manic-like symptoms, 2 of which had a history of bipolar disorder and one with manic symptoms which developed on withdrawal of desipramine. Normal subjects experienced either mild anxiety or no effect after yohimbine. Yohimbine increases anxiety in patients with mild anxiety disorder .
B) A 41-year-old male with a 3 year history of bipolar disorder presented with depressive symptoms of 1 year duration unresponsive to a 6 month trial of desipramine 250 mg/day and lithium 2100 mg/day. Lithium was discontinued. He was given a 10 mg yohimbine challenge upon hospital admission. One hour after receiving yohimbine, the patient experienced tremulousness, restlessness, giddiness, pressured speech, and feelings of increased energy and euphoria. Two hours after receiving yohimbine, he began to return to his baseline state. He continued to experienced increased energy, decreased hopelessness, and decreased depression 4 hours after the yohimbine challenge. His full depressive symptoms returned by the next morning. Following a 4 week period during which desipramine was discontinued and placebo was given, the patient's depression resolved. A second challenge of yohimbine 10 mg led to chills within 60 minutes, and within 90 minutes he reported feeling euphoric. After 2 hours he returned to his baseline state .
C) A 20-year-old female with melancholic major depression with mood-congruent psychosis during her second pregnancy was treated with desipramine 250 mg and perphenazine 40 mg daily with partial response. Perphenazine was discontinued 6 weeks postpartum and desipramine was tapered off and discontinued 5 days prior to hospital admission. After a 3-week placebo washout period, she reported hearing voices telling her to kill herself. She was given a 20 mg yohimbine challenge. Within one hour she experienced tremor, lacrimation, rhinorrhea, and became talkative. In the next 30 minutes, her affect brightened, her speech became increasingly clear and loud, and her hallucinations stopped. Depressive symptoms gradually returned over the next several hours. Bupropion was initiated at doses up to 600 mg/day, during which depression and intermittent hallucinations continued. A second challenge of yohimbine 20 mg led to mild nausea and tremulousness within 30 minutes, which resolved over an hour. Her affect improved and remained bright for several hours, after which she returned to her baseline state .
D) A 43-year-old woman with a 26-year history of bipolar disorder was discontinued from all medications prior to hospital admission (thioridazine, lithium, l-triiodothyronine, methylphenidate, and lorazepam) with the exception of trazodone which was tapered off over 5 days following admission. One hour after receiving yohimbine 20 mg orally, she became giddy, voluble, and expansive. She experienced diaphoresis, palpitations, and tremors. Her elation progressed into giggling with loud hysterical, inappropriate laughter. The intense manic symptoms persisted for 40 minutes. Her affect remained elated for the remainder of the day .
Lithium Overview
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Lithium is used to treat and prevent episodes of mania (frenzied, abnormally excited mood) in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Lithium is in a class of medications called antimanic agents. It works by decreasing abnormal activity in the brain.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.