Drug Class: 

Tricyclic Antidepressants (TCA)

Medication names: 

Clomipramine, Imipramine, Amitriptyline, Nortriptyline, Doxepin, Desipramine and more.

How they work:

Boosts the effects of the neurotransmitters serotonin and norepinephrine

What makes them unique:

This is an old class of antidepressants. Many of the medications are still in use today but they are rarely used for depression. These days, TCAs are mostly used for migraines, pain, or to help with sleep.

Side effects: 

Considered a “dirty drug”. This means that these medications bind to more than just serotonin and norepinephrine receptors. They block histamine-1 which can cause sedation and weight gain. They block muscarinic receptors which can cause dry mouth and blurred vision. They block alpha receptors which can cause low blood pressure and dizziness.

Rare side effects include seizures, cardiac arrhythmias, QTc prolongation, paralytic ileus, induction of mania, and activation of suicidal ideation in people age 24 and younger.

How effective are they:

(1) A meta-analysis compared SSRI medications with TCAs. Evidence from 102 trials with 10,706 patients were reviewed. There was no overall difference in efficacy. TCAs appear to be more effective in patients hospitalized for depression and Amitriptyline seemed to stand out as being more effective than SSRIs. The SSRIs were tolerated better and had fewer patients discontinue treatment due to side effects.

(2) A second meta-analysis also compared SSRI medications to TCAs. 11 studies with 2,951 patients were reviewed. This study found similar efficacy rates and higher side effects in the TCA group.

Clinical experience:

Not seen for depression very commonly. They still can work, but sometimes are not tolerated as well as some of the newer agents. These medications are also more dangerous in overdose than other antidepressants. This can be a big issue if the patient is suicidal or has a history of overdose. Pharmaceuticals should never be used as the sole treatment for mental illnesses. Therapy, exercise, meditation or other treatments should always accompany prescriptions.

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1. Anderson IM. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord. 2000 Apr;58(1):19-36.

2. MacGillivray S, Arroll B, Hatcher S, et al. Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis. BMJ. 2003 May 10;326(7397):1014.

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