Can I take olanzapine and amitriptyline together?

October 9, 2025 •

4 min read

In the United States, psychotropic drugs are among the most prescribed medications for adults [1.7.4]. Combining them, such as asking, 'Can I take olanzapine and amitriptyline together?', requires careful consideration of interaction risks under medical supervision [1.2.1, 1.2.2].

Quick Summary

Combining olanzapine and amitriptyline can increase risks of serious side effects, including sedation, anticholinergic effects, and heart rhythm problems. This combination should only be used under a doctor's supervision.

Key Points

Moderate Interaction: Combining olanzapine and amitriptyline has a moderately significant interaction risk and should only be done under medical supervision [1.2.1].
Increased Sedation: The combination significantly increases CNS depression, leading to excessive drowsiness, dizziness, and impaired concentration [1.6.3].
Anticholinergic Effects: Both drugs have anticholinergic properties, and taking them together enhances side effects like dry mouth, blurred vision, and constipation [1.8.2].
Cardiac Risks: There is an additive risk of QT prolongation, which can lead to serious and potentially fatal irregular heart rhythms [1.7.3].
Avoid Alcohol: Alcohol potentiates the sedative effects of this combination and should be avoided to prevent severe impairment [1.6.2].
Consult a Doctor: Never combine these medications without a doctor's prescription and guidance due to the potential for severe adverse effects [1.2.1].
Monitor Symptoms: Patients should be closely monitored for adverse effects, especially the elderly, who are more sensitive to the side effects [1.2.2].

Understanding Olanzapine and Amitriptyline

Olanzapine and amitriptyline are two distinct medications prescribed for various mental health conditions. Understanding their individual functions is crucial before exploring their combined use. Combining these medications may be done in specific clinical situations, such as for treatment-resistant depression, but it requires careful medical supervision due to significant interaction risks [1.6.5, 1.2.1].

What is Olanzapine?

Olanzapine is classified as an atypical, or second-generation, antipsychotic [1.4.1, 1.4.2]. It is primarily used to treat schizophrenia and bipolar disorder in adults and teenagers [1.4.1]. The medication works by balancing the levels of dopamine and serotonin, which are natural substances in the brain that regulate mood, thoughts, and behaviors [1.4.3, 1.4.2]. Its mechanism involves acting as an antagonist at dopamine D2 and serotonin 5HT2A receptors [1.4.2, 1.4.6]. By blocking these receptors, olanzapine can help reduce psychotic symptoms like hallucinations and delusions [1.4.4].

What is Amitriptyline?

Amitriptyline belongs to a class of drugs known as tricyclic antidepressants (TCAs) [1.5.4, 1.5.5]. It is approved for treating symptoms of depression [1.5.4]. Its primary mechanism involves blocking the reuptake of two neurotransmitters, serotonin and norepinephrine, in the brain [1.5.1]. This action increases their availability, which can help maintain mental balance and improve mood [1.5.4, 1.5.2]. Beyond depression, amitriptyline is also used off-label to prevent migraine headaches and treat certain types of chronic pain, like post-herpetic neuralgia [1.5.4].

Can I take olanzapine and amitriptyline together? The Interaction Risks

Combining olanzapine and amitriptyline is generally not recommended without explicit guidance from a healthcare professional due to a moderate, but clinically significant, drug interaction [1.2.1]. Using them together can amplify the side effects of each drug and introduce new risks. An open-label study showed that adding olanzapine to amitriptyline could be an effective augmentation strategy for treatment-resistant depression with melancholic features, but this was done in a hospitalized setting with close monitoring [1.6.5].

The primary concerns with this combination are:

Increased Central Nervous System (CNS) Depression: Both medications cause drowsiness and sedation [1.6.3, 1.2.1]. When taken together, this effect is additive, leading to excessive drowsiness, dizziness, confusion, difficulty concentrating, and impairment of judgment and motor skills [1.6.2, 1.6.4]. This significantly increases the risk of accidents, and activities requiring mental alertness, such as driving, should be avoided [1.2.1].
Enhanced Anticholinergic Effects: Both drugs possess anticholinergic properties, which block the neurotransmitter acetylcholine [1.8.3, 1.4.5]. Combining them increases the likelihood and severity of side effects like dry mouth, blurred vision, constipation, difficulty urinating, heat intolerance, and confusion [1.8.2, 1.3.3]. The elderly are particularly susceptible to these effects [1.2.2].
Risk of QT Prolongation: Both olanzapine and amitriptyline are known to have the potential to prolong the QTc interval on an electrocardiogram (ECG) [1.7.2, 1.7.1, 1.8.3]. The QTc interval represents the time it takes for the heart's ventricles to recharge between beats. A prolonged interval increases the risk of dangerous and potentially fatal irregular heart rhythms, including Torsade de Pointes and sudden death [1.7.3, 1.3.4]. The concurrent use of two or more drugs that prolong the QT interval results in additive effects, magnifying this risk [1.7.3].
Hypotension: The combination can increase the risk of hypotension (low blood pressure), particularly orthostatic hypotension, which is a drop in blood pressure upon standing that can cause dizziness and fainting [1.3.2, 1.4.5, 1.5.6].


Feature	Olanzapine (Zyprexa)	Amitriptyline (Elavil)
Drug Class	Atypical Antipsychotic [1.4.1]	Tricyclic Antidepressant (TCA) [1.5.4]
Primary Use	Schizophrenia, Bipolar Disorder [1.4.1, 1.4.3]	Depression [1.5.4]
Mechanism	Dopamine and Serotonin Antagonist [1.4.2]	Serotonin and Norepinephrine Reuptake Inhibitor [1.5.1]
Common Side Effects	Drowsiness, weight gain, dizziness, dry mouth, constipation [1.4.1]	Drowsiness, dry mouth, blurred vision, constipation, weight changes [1.5.4]
Major Interaction Risk	CNS depression, QT prolongation, anticholinergic effects [1.3.4, 1.7.2, 1.8.6]	CNS depression, QT prolongation, anticholinergic effects [1.8.3, 1.7.1]

Important Precautions and Medical Advice

Given the potential for significant interactions, several precautions are essential. Never start, stop, or alter the dosage of these medications without consulting your doctor [1.2.1].

When to Seek Medical Attention

It is crucial to inform your healthcare provider about all medications you are taking, including over-the-counter drugs, vitamins, and herbal supplements [1.2.1]. If you are prescribed both olanzapine and amitriptyline, watch for and immediately report any of the following symptoms to your doctor:

Extreme drowsiness, confusion, or memory problems [1.2.1]
Irregular, rapid, or pounding heartbeat [1.2.1]
Dizziness, lightheadedness, or fainting [1.4.1]
Severe constipation or difficulty urinating [1.8.2]
Uncontrollable muscle movements [1.4.1]
Hallucinations or severe agitation [1.2.2, 1.5.4]

Lifestyle Considerations

Alcohol: Avoid or strictly limit alcohol consumption. Alcohol can potentiate the CNS depressant effects of both medications, increasing drowsiness and impairing judgment [1.6.2, 1.2.1].
Driving: Do not drive or operate heavy machinery until you know how this combination affects you, due to the high risk of sedation and impaired coordination [1.2.1].
Heat Exposure: Be cautious in hot weather, as the combination can make it harder for your body to cool down [1.2.1].

Conclusion

While a doctor may prescribe olanzapine and amitriptyline together under specific, monitored circumstances, combining them independently is unsafe. The interaction carries a significant risk of increased side effects, including severe CNS depression, potent anticholinergic symptoms, and life-threatening cardiac arrhythmias due to QT prolongation [1.6.3, 1.8.2, 1.7.3]. Always follow your doctor’s advice and maintain open communication about any side effects you experience. The decision to use these medications in combination must weigh the potential benefits against the considerable risks, a judgment that can only be made by a qualified healthcare professional.

For more detailed drug interaction information, you can visit Drugs.com.

Frequently Asked Questions

The main risks include increased central nervous system depression (severe drowsiness, confusion), enhanced anticholinergic side effects (dry mouth, constipation, blurred vision), and a heightened risk of QT prolongation, which can cause dangerous irregular heartbeats [1.6.3, 1.8.2, 1.7.3].

No, you should avoid or limit the use of alcohol. Alcohol can significantly worsen the drowsiness and dizziness caused by both medications, leading to severe impairment of judgment and coordination [1.2.1, 1.6.2].

QT prolongation is a condition where the heart's electrical system takes longer than normal to recharge between beats. It can increase the risk of a life-threatening arrhythmia called Torsade de Pointes and sudden cardiac death [1.7.3, 1.7.6].

No, you should avoid activities that require mental alertness, such as driving or operating hazardous machinery, until you understand how the combination affects you due to the high risk of sedation and impaired psychomotor skills [1.2.1, 1.6.3].

Anticholinergic side effects result from blocking the neurotransmitter acetylcholine and can include dry mouth, blurred vision, constipation, difficulty urinating, confusion, and heat intolerance [1.8.2, 1.8.3].

Yes, side effects may be more likely to occur and be more severe in the elderly or those with a debilitating condition, particularly confusion, memory problems, and other anticholinergic effects [1.2.1, 1.2.2].

If you experience any severe side effects like irregular heartbeat, extreme drowsiness, confusion, hallucinations, or difficulty breathing, you should contact your doctor immediately [1.2.1, 1.2.2].