Can Mood Stabilizers Trigger Psychosis? Understanding the Risks and Rare Occurrences

October 11, 2025 •

4 min read

According to case studies and reports, psychosis is a rare but documented adverse event associated with mood stabilizer treatment in some individuals, particularly with medications like lamotrigine. This critical question—can mood stabilizers trigger psychosis?—highlights the complex interplay between medication effects, individual neurobiology, and underlying psychiatric conditions.

Quick Summary

This article explores the documented cases where mood stabilizers can induce psychotic symptoms, distinguishing between rare paradoxical reactions, toxicity, and medication withdrawal. It covers specific risks associated with lithium, valproate, and lamotrigine, and emphasizes the importance of clinical monitoring and managing underlying vulnerabilities.

Key Points

Rare Occurrence: It is rare for mood stabilizers to trigger psychosis directly, but documented cases exist for certain medications and in specific situations.
Toxicity Risk: Lithium toxicity, which can occur even in the therapeutic range, can cause severe neurological symptoms, including psychosis.
Delirium vs. Psychosis: Valproate can cause hyperammonemic delirium, which may be mistaken for psychosis or worsening mania and is reversible upon discontinuation.
Withdrawal Psychosis: Abruptly stopping a mood stabilizer can lead to "rebound psychosis," a withdrawal effect that can be more severe than the initial symptoms.
Paradoxical Reactions: In some vulnerable individuals, a mood stabilizer might act paradoxically or unmask an underlying predisposition to psychosis.
Clinical Evaluation is Crucial: Distinguishing a drug side effect from the progression of an underlying illness requires careful medical evaluation and consideration of the timing of symptom onset.

The Complex Relationship Between Mood Stabilizers and Psychosis

For most individuals, mood stabilizers are an essential treatment for managing conditions like bipolar disorder, which may involve periods of psychosis. These medications are typically used to prevent or reduce the severity of mood episodes, including manic episodes that can include psychotic features such as hallucinations or delusions. Therefore, the occurrence of psychosis during treatment with a mood stabilizer is often unexpected and warrants immediate clinical investigation.

The key to understanding this phenomenon lies in distinguishing several possible scenarios:

Medication-Induced Psychosis or Delirium: A direct side effect of the drug or an adverse reaction to a toxic level.
Paradoxical Reaction: The medication produces an effect opposite to what is expected, unmasking an underlying vulnerability to psychosis.
Underlying Condition: The psychosis is part of the patient's existing illness, perhaps a breakthrough episode, rather than caused by the medication.
Withdrawal Psychosis: A rebound effect that occurs upon the abrupt discontinuation of the medication.

Specific Mood Stabilizers and Psychosis Risk

While the risk is not universal across all mood stabilizers, specific medications have documented, albeit rare, associations with psychotic symptoms.

Lithium

In cases of lithium toxicity, which can occur even within the therapeutic range, severe neurological symptoms may manifest. These can include psychosis, along with other symptoms such as movement disorders, memory problems, and confusion. A 1986 report described six cases of manic-depressive psychosis patients who developed neurological sequelae, including psychosis, following lithium treatment. This underscores that while lithium is a cornerstone for treating bipolar disorder, monitoring for toxicity is crucial to prevent severe side effects.

Valproic Acid (VPA)

Valproate is another common mood stabilizer associated with rare, severe adverse effects. One notable risk is valproate-induced hyperammonemic delirium, which can produce symptoms that mimic psychosis or a worsening of mania. Elevated plasma ammonia levels are the cause, and symptoms typically resolve after the drug is discontinued. Additionally, cases of VPA-induced behavioral disturbances, including hallucinations and hyperactivity, have been reported. The exact mechanism is not fully understood but may involve an increase in the brain's GABA levels. Clinicians should monitor plasma ammonia levels in patients taking valproate who develop altered mental states to rule out this potentially severe side effect.

Lamotrigine

Several case reports have described patients, including those with bipolar disorder and no prior history of epilepsy or psychosis, who developed psychotic symptoms or hallucinations after starting lamotrigine. A series of six cases reported in Epilepsy & Behavior noted that while rare, psychosis can be an adverse event of lamotrigine treatment, with potential risk factors including psychiatric comorbidity or temporal lobe pathology. The exact mechanism is unclear, but one hypothesis suggests that lamotrigine's inhibitory effect on glutamate release could play a role. Unlike toxicity-induced psychosis, these reports often describe dose-dependent effects, with symptoms resolving upon dose reduction or discontinuation.

Abrupt Discontinuation: A Critical Cause of "Rebound Psychosis"

One of the most significant—and often misunderstood—reasons a patient might experience psychosis related to medication is abrupt withdrawal. This is particularly noted with antipsychotics but also applies to mood stabilizers, which can impact dopamine and other neurotransmitter systems. When a medication is suddenly stopped, the brain's neurochemistry can become dysregulated, leading to a severe rebound of symptoms, sometimes more intense than before treatment began. Abrupt discontinuation of lithium, for example, is known to increase relapse risk. This phenomenon, sometimes called "dopamine supersensitivity psychosis," reinforces the necessity of gradual tapering under medical supervision.

Distinguishing Medication Effects from an Underlying Condition

For clinicians, determining whether new psychotic symptoms are due to medication or the underlying illness is a complex but vital process. A detailed history, including the timing of symptoms relative to dose changes or discontinuation, is critical. The clinical picture is also important; for example, delirium associated with valproate toxicity might differ from a typical manic-psychotic episode. In individuals with underlying vulnerabilities, a medication might act as a catalyst, unmasking or triggering symptoms that were already predisposed to occur.

Factors Influencing Medication-Related Psychosis Risk:

Individual Neurobiology: Unique brain chemistry can influence how a person responds to a drug.
Genetic Predisposition: Family history of bipolar disorder or other psychotic conditions can increase vulnerability.
Comorbid Conditions: Co-occurring psychiatric or neurological issues may increase risk.
Toxicity and Dosage: High or toxic drug levels are a known trigger, especially with lithium.
Abrupt Withdrawal: The sudden cessation of medication can cause a severe rebound effect.

Comparing Psychosis Risk in Mood Stabilizers


Mood Stabilizer	Associated Psychosis Risk	Mechanism (if known)	Notes
Lithium	Severe Toxicity	Neurological damage at toxic levels.	Psychosis is a sign of medical emergency due to toxicity; often accompanied by other neurological signs.
Valproate (VPA)	Rare, associated with delirium	Hyperammonemia or elevated GABA.	Symptoms resemble psychosis but are a form of delirium; reversible upon discontinuation.
Lamotrigine	Very Rare, idiosyncratic	Possibly inhibitory effect on glutamate.	Documented in specific case reports, often reversible upon dose reduction or withdrawal.
Atypical Antipsychotics (used as stabilizers)	Minimal (as side effect)	N/A	Typically prescribed to prevent psychosis, not cause it; withdrawal can be a risk.

Conclusion

While mood stabilizers are generally effective in preventing psychosis in conditions like bipolar disorder, documented evidence shows that they can, in rare circumstances, trigger or contribute to psychotic symptoms. This can occur due to toxicity (e.g., lithium), paradoxical reactions (e.g., lamotrigine), or as part of a delirium state (e.g., valproate). The most common risk, however, is rebound psychosis resulting from abrupt medication discontinuation. For patients and clinicians, maintaining vigilant communication and careful monitoring for changes in mental state is paramount. If psychotic symptoms emerge during treatment, a thorough medical evaluation is necessary to distinguish between an adverse drug reaction and the progression of the underlying illness. For more information, resources like StatPearls offer detailed reviews on medication-induced conditions, such as substance-induced mood disorders.

Note: This article is for informational purposes and is not a substitute for professional medical advice. Always consult a healthcare provider for diagnosis and treatment.

Frequently Asked Questions

The risk is generally very low. However, cases of psychotic symptoms have been documented with lithium (due to toxicity), valproate (often as delirium), and lamotrigine (rare, idiosyncratic reactions).

It is possible but extremely rare. In some cases, a medication may 'unmask' an underlying vulnerability to psychosis that was previously unknown. Abrupt discontinuation is also a more common trigger for rebound psychosis.

Medication-induced psychosis is a direct adverse effect of the drug, often resolving with discontinuation or dose adjustment. A psychotic episode from an illness is a symptom of the disease itself. A clinician must evaluate the timing and nature of the symptoms to distinguish between the two.

Yes. The sudden cessation of a mood stabilizer, especially with abrupt discontinuation, can cause a severe withdrawal or rebound effect, leading to psychotic symptoms. This is a primary reason why medication should only be tapered gradually under a doctor's supervision.

Contact your prescribing doctor immediately. Do not stop taking the medication on your own. Hallucinations could be a symptom of toxicity, a rare adverse reaction, or an underlying condition, and require prompt medical evaluation.

Not necessarily. Psychosis risk depends on the specific medication and its mechanism, rather than its age. For example, lithium toxicity risk is well-documented, while lamotrigine's psychosis risk is tied to very rare idiosyncratic reactions.

Clinicians monitor for symptoms at initiation and with any dose changes. For drugs like lithium, they regularly check blood levels to prevent toxicity. They also assess for subtle changes in behavior, cognition, and mood that could indicate an adverse reaction.