Which of the following are important side effects of tetrabenazine: depression, anxiety, suicidal or homicidal ideation, hallucinations, or obsessive‑compulsive disorder?

Important Side Effects of Tetrabenazine

Depression and suicidal ideation are the most critical side effects of tetrabenazine, carrying an FDA black-box warning that contraindicates its use in patients who are depressed or have suicidal thoughts. 1

FDA Black-Box Warning and Contraindications

The FDA drug label explicitly states that tetrabenazine is contraindicated in patients who are depressed or have thoughts of suicide. 1 The medication guide warns that depression, suicidal thoughts, or suicidal actions are serious side effects requiring immediate medical attention. 1

Do not prescribe tetrabenazine to patients with:

• Active depression 1
• Current suicidal ideation 1
• History of suicidal thoughts or suicide attempts 1
• Emotional or mental problems including nervousness, anxiety, anger, agitation, or psychosis 1

Depression and Suicidality: Evidence vs. Warning

Despite the black-box warning, recent observational evidence presents a more nuanced picture:

Real-world data from closely monitored patients:

• In the large Enroll-HD database study (n=4,091), tetrabenazine users actually had a lower risk of suicidality (OR = 0.61, p = 0.043) compared to non-users 2
• Among patients with a history of depression, tetrabenazine users had lower incidence of both depression (OR = 0.71, p = 0.016) and suicidal ideation (OR = 0.57, p = 0.028) 2
• A prospective study of 1,360 Huntington's disease patients found no increased risk of depressed mood (HR = 0.9-1.2) or suicidal ideation (HR = 0.5-0.6) with tetrabenazine exposure 3
• Zero suicide attempts or completed suicides occurred among tetrabenazine-exposed patients in this cohort, compared to 17 attempts (1.4%) and 4 suicides (0.3%) in unexposed patients 3

However, the FDA contraindication must be respected in clinical practice because these studies involved close clinical supervision and careful patient selection, excluding those with active depression at baseline. 1, 3

Anxiety and Agitation

Anxiety is listed as a common side effect in the FDA label, along with restlessness and agitation. 1 Patients should be monitored for nervousness and anxiety as part of their baseline assessment and ongoing care. 1

Akathisia (Restlessness)

Akathisia—a condition of severe inner restlessness with a strong urge to move—is a recognized adverse effect of tetrabenazine. 1 This extrapyramidal symptom is dose-limiting and typically reversible with dosage reduction. 4, 5

Hallucinations

Hallucinations are not listed as a common or serious side effect in the FDA drug label for tetrabenazine. 1 While the label mentions that patients with psychosis should inform their doctor before starting treatment, hallucinations are not identified as an expected adverse event. 1

Obsessive-Compulsive Disorder

OCD is not listed as a side effect of tetrabenazine in the FDA label or in clinical literature. 1 There is no evidence that tetrabenazine induces or worsens obsessive-compulsive symptoms.

Other Serious Psychiatric Side Effects

Beyond the primary concerns, tetrabenazine can cause:

• Neuroleptic Malignant Syndrome (NMS): A potentially fatal reaction requiring immediate emergency care 1
• Parkinsonism: Tremor, rigidity, bradykinesia, and balance problems 1, 4
• Sedation: A very common dose-limiting effect 1, 4, 5

Clinical Monitoring Algorithm

Before prescribing tetrabenazine:

1. Screen for current depression, suicidal ideation, or history of suicide attempts 1
2. Assess for anxiety, nervousness, agitation, anger, or psychosis 1
3. Document psychiatric history thoroughly 1

During treatment:

1. Monitor for new or worsening depression at every visit 1
2. Directly ask about suicidal thoughts, plans, or intent 1
3. Watch for increased anxiety, agitation, restlessness, or akathisia 1
4. Assess for sedation and parkinsonism 1
5. Reduce dose if psychiatric symptoms emerge 4, 5

Instruct patients and families to report immediately:

• New or worsening thoughts of death or suicide 1
• Self-destructive behavior 1
• Increased anxiety, panic, agitation, or aggression 1
• Increased impulsivity 1
• Severe restlessness or inability to sit still 1

Summary of Side Effects by Category

Important side effects confirmed by FDA label:

• Depression (black-box warning, contraindication) 1
• Suicidal ideation (black-box warning, contraindication) 1
• Anxiety (common side effect) 1
• Restlessness/akathisia (serious side effect) 1

NOT established as side effects:

• Homicidal ideation (not mentioned in FDA label) 1
• Hallucinations (not listed as side effect) 1
• OCD (not listed as side effect) 1