Tetrabenazine Side Effects: What to Expect and When to Call Your Doctor

Tetrabenazine (brand name Xenazine) is an effective treatment for chorea in Huntington's disease, but it comes with a significant side effect profile that patients and caregivers need to understand. This guide covers Tetrabenazine's most important side effects — from the boxed warning for depression and suicidality to common issues like sedation and parkinsonism — and tells you exactly when to call your doctor.

The Boxed Warning: Depression and Suicidal Thinking

This is Tetrabenazine's most serious risk. The FDA requires a boxed warning — its highest level of safety warning — for Tetrabenazine because it increases the risk of depression and suicidal thoughts and behavior in patients with Huntington's disease.

In clinical trials, 19% of patients treated with Tetrabenazine developed or had worsening depression compared to none in the placebo group. In longer open-label studies (up to 80 weeks), the rate was 35%. Tetrabenazine is contraindicated in patients who are actively suicidal and in those with untreated or inadequately treated depression.

Call 911 or go to the emergency room immediately if you or someone taking Tetrabenazine expresses thoughts of self-harm or suicide.

Common Side Effects (Affect More Than 5% of Patients)

The following side effects are commonly reported with Tetrabenazine. Many improve as your body adjusts, but monitor them closely:

Somnolence and sedation: Tetrabenazine can cause significant drowsiness. Do not drive or operate machinery until you know how it affects you. Avoid alcohol and other CNS depressants.

Depression: Mood changes, feelings of hopelessness, or worsening of existing depression. Report any mood changes to your neurologist promptly.

Anxiety and nervousness: A sense of agitation or worry that is more than usual.

Nausea: Usually mild and may improve with time. Taking Tetrabenazine with food (though not required) may help.

Akathisia (restlessness): A feeling of inner restlessness or an irresistible urge to move. Call your doctor if this develops.

Insomnia: Difficulty falling or staying asleep, paradoxically alongside daytime sedation.

Parkinson-Like Symptoms: Parkinsonism

Because Tetrabenazine depletes dopamine — the same neurotransmitter that is depleted in Parkinson's disease — it can cause Parkinson-like motor symptoms (parkinsonism) including:

Tremors or shaking

Muscle stiffness and rigidity

Slowed movement (bradykinesia)

Balance problems and falls

Drooling

Call your doctor right away if you develop new parkinsonism symptoms. Your dose may need to be reduced.

Serious Side Effects: Seek Immediate Medical Attention

Neuroleptic Malignant Syndrome (NMS): A rare but life-threatening reaction. Symptoms include very high fever, severe muscle rigidity, fast or irregular heartbeat, sweating, confusion. Stop Tetrabenazine and seek emergency care immediately if these occur.

QT prolongation: Tetrabenazine can cause a small prolongation of the QT interval (about 8 milliseconds), which in susceptible individuals can lead to torsade de pointes, a dangerous heart rhythm. Risk is higher if you take other QT-prolonging medications, have low potassium or magnesium, or have a history of cardiac arrhythmias.

Orthostatic hypotension: A sudden drop in blood pressure when standing. Can cause dizziness and fainting. Rise slowly from sitting or lying positions.

Dysphagia: Difficulty swallowing, which can increase aspiration risk in HD patients who already have swallowing problems.

When to Call Your Doctor About Tetrabenazine Side Effects

Call your neurologist (non-emergency) if you notice:

Worsening depression or mood changes

New or worsening tremor, stiffness, or movement problems

Persistent sedation affecting daily function

Inner restlessness or akathisia

Also important: many side effects can be worsened by drug interactions. Read our guide: Tetrabenazine Drug Interactions: What to Avoid.