What are the most commonly used drugs for depression?

The most common include SSRIs, SNRIs, tricyclic antidepressants, MAO inhibitors, lithium, and some atypical antipsychotics as adjuncts.

Which drug is best for treatment-resistant depression?

For resistant depression, lithium augmentation, MAOIs, or combination strategies may be effective, under psychiatric supervision.

Which antidepressants have fewer side effects?

Second-generation antidepressants, particularly SSRIs and SNRIs, tend to have better tolerability and a favorable safety profile.

Can medications be combined with psychotherapy?

Yes, combined treatment is often more effective than monotherapy, especially in moderate to severe depression.

Which antidepressants are risky for older adults?

TCA and MAOIs should be used with caution or avoided in the elderly due to cardiovascular and cognitive risks. SSRIs are generally preferred.

Antidepressant Medications: Comparative Table, Mechanisms and Clinical Uses

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Summary Table of the Main Pharmacological Treatments for Depression

Drug	Mechanism of Action	Indications	Contraindications	Advantages	Disadvantages
Tricyclic Antidepressants (TCAs)	Inhibit reuptake of norepinephrine and serotonin; also affect cholinergic, histaminergic, and adrenergic receptors.	Major depression, neuropathic pain, anxiety disorders; used in monotherapy or combination (requires close monitoring).	Cardiopathies, glaucoma, prostatic hypertrophy, high suicidal risk.	Powerful antidepressant effect; also effective for somatic symptoms and pain.	Wide and complex side effect profile; risk of cardiac toxicity.
Monoamine Oxidase Inhibitors (MAOIs)	Irreversibly or reversibly inhibit monoamine oxidases, increasing synaptic monoamine levels.	Atypical or treatment-resistant depression, hypersomnia, hyperphagia; used in monotherapy or in combination with psychotherapy.	Poor dietary compliance, severe drug interactions (hypertensive crisis with tyramine).	Effective in non-responders to other antidepressants.	Complex management; requires strict diet and close monitoring.
Second-Generation Antidepressants	Act selectively on receptors and transporters (SSRIs, SNRIs, NaSSA, NDRI); improved tolerability and safety.	Unipolar depression, dysthymia, anxiety; first-line as monotherapy or combination with psychotherapy.	Drug hypersensitivity, uncontrolled epilepsy, concurrent use with MAOIs.	Good tolerability, low toxicity; strong clinical evidence base.	Delayed onset, possible initial anxiety activation; sexual dysfunction.
Antidepressant-Acting Antipsychotics (Neuroleptic)	Modulate dopamine and serotonin (D2/5-HT2A antagonism); some have mood-stabilizing activity.	Depression with agitation, psychotic or resistant features; used only in combination with antidepressants.	Metabolic syndrome, prolonged QT, extrapyramidal risk.	Enhance antidepressant effect; effective for psychotic or mixed symptoms.	Weight gain, sedation, metabolic and neurological risks.
Lithium Salts	Modulate intracellular signaling (second messengers) and neuroplasticity; stabilize mood.	Bipolar depression, high suicide risk, antidepressant augmentation; used in combination.	Renal failure, hypothyroidism, dehydration, pregnancy.	Reduces suicide risk; effective in resistant and bipolar forms.	Requires constant monitoring; risk of renal and thyroid toxicity.

References

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Kennedy SH et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder. Can J Psychiatry. 61(9), 2016: 540–560.
Cleare A et al. Evidence-based guidelines for treating depressive disorders with antidepressants. J Affect Disord. 191, 2016: 86–122.
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Fiedorowicz JG et al. Monoamine oxidase inhibitors: a modern review. Expert Opin Pharmacother. 11(18), 2010: 2957–2968.
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McIntyre RS et al. The role of atypical antipsychotics in the treatment of major depressive disorder. CNS Drugs. 28(9), 2014: 817–827.
Malhi GS et al. Lithium therapy for bipolar disorder and major depression: a review of current literature. Aust N Z J Psychiatry. 51(3), 2017: 190–206.
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