Depression is associated with reduced levels of key neurotransmitters in the brain: serotonin, dopamine, and noradrenaline. These chemicals are involved in regulating mood, motivation, and emotional stability. Major classes include: Selective Serotonin Reuptake Inhibitors (SSRIs) Serotonin–Noradrenaline Reuptake Inhibitors (SNRIs) Monoamine Oxidase Inhibitors (MAOIs) Tricyclic Antidepressants (TCAs) Lithium (used mainly as a mood stabilizer in bipolar disorder) Separate articles cover each class in detail. The following article will provide an introduction to depression and cover general information regarding drug therapy to treat depression. Delay In Onset Of Effect An improvement in a patient’s depressive condition may not occur during the first few weeks or more of treatment. Early in therapy, the risk of suicide may temporarily increase, as energy and motivation improve before mood stabilizes. Close monitoring is essential during early treatment and after dose adjustments — especially for worsening depression, suicidal thoughts, or behaviour. A meta-analysis of placebo-controlled trials found that patients under 25 years old had an increased risk of suicidal behaviour when taking antidepressants compared to placebo. Withdrawal Syndrome Doses of all antidepressants should be gradually reduced over at least 1-2 weeks to reduce risk of withdrawal effects. Withdrawal symptoms include: Dizziness Sleep disturbance Agitation or anxiety Nausea and/or vomiting Tremor Headache These symptoms usually occur within the first few days of discontinuing treatment and resolve within 2 weeks (but effect can be prolonged for 2-3 months or more). Withdrawal effects are more likely with drugs that have a short half-life, such as venlafaxine (half-life ~5 ± 2 hours), compared to drugs like fluoxetine, which has a long half-life (4–6 days) and a gradual washout period. Serotonin Syndrome Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity, often due to drug interactions. The most severe cases of serotonin syndrome generally involve an MAOI which impairs the metabolism of serotonin. Clinical Features: Confusion, agitation, or delirium Sweating and shivering Fluctuating blood pressure Muscle rigidity or myoclonus Hyperthermia (in severe cases) Severe serotonin syndrome can resemble Neuroleptic Malignant Syndrome (NMS), with high fever, rigidity, and autonomic instability. The following drugs used concomitantly can increase risk of serotonin syndrome: SSRIs SNRIs All MAOIs: moclobemide, linezolid, selegiline, methylene blue Lithium Tramadol TCAs: clomipramine or amitriptyline Pethidine Triptans Sibutramine St John’s Wort Serotonin precursors such as tryptophan supplements Adobe stock: 242094882 Fig 1: Mechanism and symptoms of serotonin syndrome Summary Table Key Point Description Neurotransmitters involved Serotonin, dopamine, noradrenaline Main antidepressant classes SSRIs, SNRIs, MAOIs, TCAs, Lithium Onset of effect Delayed (2–4 weeks) Withdrawal risk Higher with short half-life drugs (e.g. venlafaxine) Serotonin syndrome risk Increased by combining serotonergic agents Monitor for Suicidal thoughts in early treatment Do you think you’re ready? Take the quiz below Pro Feature - Quiz Depression Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePharmacy Pro Challenge yourself with over 2100 multiple-choice questions to reinforce learning Learn More Rate This Article