Depression and anxiety: biology and drug treatment
What is thought to go wrong in the brain in depression and anxiety, and how antidepressants and other medicines are used and monitored.
Depression and anxiety disorders are common and often occur together. Genetic, biological, environmental and psychological factors all contribute. Drug treatment works best as part of care that includes psychotherapy, and it needs patience: most antidepressants take weeks to reach full effect.
Symptoms
Major depression goes beyond sadness: low mood or loss of interest with changes in sleep, appetite, energy, concentration and self-worth, sometimes with thoughts of death. Anxiety disorders include generalised anxiety, panic disorder, social anxiety, phobias, and the related obsessive-compulsive and post-traumatic stress disorders. Both conditions impair work, study and relationships.
Neurobiology: from monoamines to neuroplasticity
Most antidepressants raise synaptic serotonin, noradrenaline or both soon after dosing starts, by blocking reuptake or breakdown. Yet the clinical response lags, which points to slower adaptive changes: altered receptor sensitivity, changes in intracellular signalling and gene expression, and increased brain-derived neurotrophic factor (BDNF), which supports dendritic spines, new synapses and neurogenesis in the hippocampus. Rapid-acting treatments support the plasticity idea: ketamine blocks NMDA receptors on inhibitory interneurons, producing a burst of glutamate release that ends up acting on AMPA receptors and BDNF.
Choosing an antidepressant
- SSRIs and SNRIs: usual first choices for depression and for panic and social anxiety disorder.
- Atypical antidepressants (bupropion, mirtazapine, trazodone) when side-effect profile matters.
- Tricyclics and MAO inhibitors: effective but more side effects and interactions; used in selected cases.
- Buspirone: for generalised anxiety; it needs daily use for weeks and does not work as needed.
- Benzodiazepines: short-term relief of severe anxiety only, because of tolerance and dependence.
Onset, response and safety
Effects usually begin within one to two weeks and can take up to about eight weeks to be complete. After a response, treatment usually continues for months to prevent relapse, and stopping is planned with a gradual taper to avoid discontinuation symptoms (dizziness, sleep problems, irritability, «brain zaps»). Children, teenagers and young adults may have more suicidal thoughts early in treatment or after a dose change, so close monitoring is advised. Combining serotonergic drugs (triptans, St John's wort, other antidepressants) can cause serotonin syndrome.
When the first drug does not work
- Check adherence, dose, duration and diagnosis (including bipolar disorder) first.
- Switch to another antidepressant, within or across classes.
- Augment: some second-generation antipsychotics (aripiprazole, quetiapine, or olanzapine with fluoxetine) are approved add-ons in treatment-resistant depression.
- Esketamine nasal spray, given in a clinical setting, is approved for treatment-resistant depression.
- Non-drug options: psychotherapy and brain stimulation therapies.
- Newer mechanisms: neurosteroids such as brexanolone act through GABA signalling rather than monoamines.
Test yourself
Think of the answer, then tap the question to see it.
What observation weakens a pure monoamine explanation of depression?
Antidepressants raise synaptic monoamines soon after dosing starts, yet the clinical response takes weeks, suggesting slower adaptive changes.
What is BDNF thought to do in antidepressant response?
It supports dendritic spine formation, new synapses and hippocampal neurogenesis, restoring neural plasticity.
Which group needs particular monitoring for suicidal thoughts at the start of antidepressant treatment?
Children, teenagers and young adults under 25, especially early in treatment or after a dose change.
How does ketamine differ from classic antidepressants?
It blocks NMDA glutamate receptors and produces rapid antidepressant effects, instead of needing weeks like monoamine-based drugs.
Example drugs
- Sertraline
- Fluoxetine
- Escitalopram
- Venlafaxine
- Bupropion
- Mirtazapine
- Buspirone
- Ketamine
- Brexanolone
- Zuranolone
Connections
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Mental Health Medications - National Institute of Mental Health (NIMH) (National Institute of Mental Health, 2026); Antidepressants - NHS (NHS (UK), 2026); Depression - National Institute of Mental Health (NIMH) (National Institute of Mental Health, 2026).
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Representative model, for educational purposes only.