Amitriptyline And Alcohol

Amitriptyline is a tricyclic antidepressant (TCA) primarily used to treat major depressive disorder and reduce nerve pain (you can read about its nerve pain reducing effects here). Like all medications, amitriptyline has potential interactions (more here), and one of the most significant interactions to be aware of is with alcohol.

The interaction between amitriptyline and alcohol is primarily pharmacodynamic, meaning it involves the combined effects of the two substances on the body's systems, rather than how the body processes each drug (pharmacokinetics). The major concerns arise from the following synergistic effects:

Central Nervous System Depression

• Both amitriptyline and alcohol depress the central nervous system. Amitriptyline, through its effects on serotonin, norepinephrine, and histamine receptors, can cause sedation and drowsiness. While, alcohol, depresses the CNS through its amplification of gamma-aminobutyric acid’s (GABA) inhibitory effect.

• As amitriptyline already causes some baseline sedation (more on that here), when combined with alcohol, there is a synergistic effect meaning the CNS depressant effect are amplified, in fact they are greater than the sum of the individual effects of both compounds.

• This can lead to an increased risk of blackouts, falls, respiratory depression, impaired protective reflexes such as the gag reflex (increasing risk of choking if you vomit) and cognitive impairment.

Increased Anticholinergic Effects (more about these effects here)

• Amitriptyline is a muscarinic acetylcholine receptor antagonist, meaning it inhibits the normal functioning of acetylcholine at these receptors. The effect of this is confusion, drowsiness, and cognitive impairment.

• Alcohol - although it does not have strong anticholinergic properties – when combined with amitriptyline can worsen the anticholinergic side effects of the medication, due to its own neurotransmitter disruption.

• This is particularly concerning in elderly patients or those with pre-existing conditions that make them more susceptible to anticholinergic effects.

Memory and learning

• Amitriptyline has been shown to impair short-term memory and learning. This due to its anticholinergic effects.

• Alcohol can potentiate these effects, as it suppresses hippocampal activity – the area of the brain responsible for memory formation - leading to more pronounced cognitive deficits.

• The combined effect of these two compounds is profound memory impairment.

Cardiovascular Effects

• The combination of amitriptyline and alcohol can also impact cardiovascular function.

• Amitriptyline blocks alpha-adrenergic receptors, leading to reduced blood pressure. While Alcohol is known to cause acute vasodilation – widening of blood vessels – which can lead to a temporary drop in blood pressure. When combined this can increase your risk of orthostatic hypotension, which can manifest as dizziness, light headedness, and fainting, particularly when standing up quickly.

• Alcohol can lead to reflex tachycardia – which is a reflex reaction in response to alcohol induced vasodilation – that can cause an increased heart rate. When this is combined with antagonism at muscarinic acetylcholine receptors, which can reduced parasympathetic control of the heart ultimately causing tachycardia. This may manifest as palpitations, and arrhythmias.

Reduced Liver Metabolism

• Amitriptyline and alcohol compete for the same liver enzymes for their metabolism. Namely, the CYP2D enzyme, part of the cytochrome p450 family.

• Alcohol can inhibit liver enzymes responsible for metabolizing amitriptyline, this leads to an increased level of amitriptyline in the blood, which can exacerbate side effects and prolong the drug's effects

What studies have investigated the effects of amitriptyline with alcohol?

There have many studies that have investigated the deleterious

• Seppälä et al (1975) in their double blind crossover study, found that amitriptyline combined with alcohol significantly increased cumulative choice reaction times, while doxepin with alcohol increased both reaction times and inaccuracy. This study highlights the real risk combining these two presents to patients, especially those are drivers.

• Allen and Lader (1989) found similar effects in their double blind cross over study. Wherein they found combining alcohol with amitriptyline can lead to significant psychomotor performance.

• Weathermon and Crabb (1999) in their review article confirmed the additive effects mentioned throughout this post. In that, alcohol consumption increases the risk of sedation and can increase your risk of orthostatic hypotension.

How to manage the risk

The overwhelming consensus is that combining alcohol with amitriptyline not recommended and therefore should be avoided.

Conclusion

Amitriptyline is an effective medication for various conditions, but its interaction with alcohol is a serious concern. The pharmacodynamic synergy between the two substances can lead to significant CNS depression, orthostatic hypotension and impaired memory, posing a substantial risk to your safety.

If you are worried about the side effects of your pain medication, you can consult with me here.

References

1. Seppälä, T., Linnoila, M., Elonen, E., Mattila, M. J., & Mäki, M. (1975). Effect of tricyclic antidepressants and alcohol in psychomotor skills related to driving. Clinical Pharmacology and Therapeutics, 17(5), 515–522. https://doi.org/10.1002/cpt1975175515

2. Weathermon, R., & Crabb, D. W. (1999). Alcohol and Medication Interactions. Alcohol Research & Health, 23(1), 40.

3. Allen, D., & Lader, M. (1989). Interactions of alcohol with amitriptyline, fluoxetine and placebo in normal subjects. International Clinical Psychopharmacology, 4 Suppl 1, 7–14. https://pubmed.ncbi.nlm.nih.gov/2783702/

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