Treating Depression: Antidepressants

Antidepressants are medications used to treat depression by altering the balance of neurotransmitters in the brain. They are one of the most commonly prescribed treatments for depression and are based on the biological approach — the idea that depression is caused by chemical imbalances in the brain.

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How Antidepressants Work

Most antidepressants work by increasing the availability of certain neurotransmitters (especially serotonin) in the synapse:

SSRIs (Selective Serotonin Reuptake Inhibitors)

SSRIs are the most commonly prescribed type of antidepressant. Examples include fluoxetine (Prozac), sertraline (Zoloft), and citalopram.

How they work:

1. Normally, after serotonin is released into the synapse, it is reabsorbed (reuptake) by the pre-synaptic neuron
2. SSRIs block the reuptake of serotonin, preventing it from being reabsorbed
3. This leaves more serotonin available in the synapse
4. The increased serotonin stimulates the post-synaptic neuron more effectively
5. Over time (usually 4–6 weeks), this increased serotonin activity improves mood

SNRIs (Serotonin-Noradrenaline Reuptake Inhibitors)

SNRIs work similarly to SSRIs but also block the reuptake of noradrenaline, increasing the availability of two neurotransmitters. Examples include venlafaxine and duloxetine.

Tricyclic Antidepressants (TCAs)

TCAs are an older class of antidepressants that block the reuptake of serotonin and noradrenaline. They tend to have more side effects than SSRIs and are now less commonly prescribed as first-line treatments. Example: amitriptyline.

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Effectiveness of Antidepressants

Evidence for Effectiveness

Study	Finding
Kirsch et al. (2008)	Meta-analysis found that antidepressants were more effective than placebo for severe depression but showed only a small advantage for mild to moderate depression
NICE guidelines	UK National Institute for Health and Care Excellence recommends antidepressants for moderate to severe depression

Are Antidepressants Always Effective?

• Antidepressants do not work for everyone — approximately 30–40% of people do not respond to the first antidepressant they try
• They typically take 4–6 weeks to start working — this delay can be difficult for patients
• Some people respond better to one type of antidepressant than another
• They are generally more effective when combined with psychological therapy (e.g. CBT)

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Side Effects

All antidepressants can cause side effects, which vary by type:

Type	Common Side Effects
SSRIs	Nausea, headache, insomnia or drowsiness, sexual dysfunction, weight changes
SNRIs	Similar to SSRIs plus increased blood pressure, dizziness
TCAs	Dry mouth, blurred vision, constipation, drowsiness, weight gain, heart rhythm problems

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Evaluation of Antidepressants

Strengths

• Effective for many people, especially those with moderate to severe depression
• Supported by extensive research and clinical trials
• Widely available and relatively inexpensive
• Can provide rapid symptom relief (compared to therapy, which takes longer)
• Allow people to function better while they develop coping strategies (often combined with therapy)

Weaknesses

• Side effects can be unpleasant and may reduce compliance (patients stop taking them)
• They treat symptoms rather than addressing the underlying causes of depression
• Withdrawal symptoms can occur when stopping antidepressants suddenly
• The delay before they take effect (4–6 weeks) is a limitation
• They are less effective for mild depression than for moderate/severe depression
• There is debate about the placebo effect — some improvement may be due to the expectation of getting better rather than the drug itself
• Long-term dependency — some patients remain on antidepressants for years

Exam Tip: When evaluating antidepressants, compare them with psychological treatments (e.g. CBT). Antidepressants treat symptoms quickly but don't address underlying causes; CBT addresses causes but takes longer to work. The best approach often combines both.

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Key Points

• Antidepressants work by increasing neurotransmitter availability (especially serotonin) in the synapse.
• SSRIs are the most commonly prescribed type — they block serotonin reuptake.
• They are effective for moderate to severe depression but less so for mild depression.
• Side effects, delayed onset, and symptom-focused treatment are limitations.
• Best results are often achieved by combining antidepressants with psychological therapy.

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The Monoamine Hypothesis

Most antidepressants are based on the monoamine hypothesis — the idea that depression is linked to low levels of monoamine neurotransmitters, particularly:

• Serotonin — involved in mood, sleep and appetite
• Noradrenaline — involved in arousal, alertness and response to stress
• Dopamine — involved in reward, motivation and pleasure

Antidepressants are designed to increase the availability of these neurotransmitters at the synapse, with the aim of restoring more balanced brain function over several weeks. Evidence for the monoamine hypothesis includes:

• Drugs that deplete monoamines (such as reserpine) can induce depressive symptoms
• Post-mortem studies sometimes find reduced serotonin-related activity in people who died by suicide
• SSRIs are clinically effective for moderate to severe depression in large trials

However, the monoamine hypothesis is incomplete. The delay in clinical effect (4–6 weeks after serotonin levels rise within hours) suggests that downstream changes in receptor sensitivity and neural plasticity — not just raw neurotransmitter levels — are involved. Modern accounts therefore treat monoamines as one part of a wider biological picture.

flowchart TD
  A[Monoamine hypothesis] --> B[Serotonin: mood, sleep, appetite]
  A --> C[Noradrenaline: arousal, alertness]
  A --> D[Dopamine: reward, motivation]
  B --> E[Low levels linked to depression]
  C --> E
  D --> E
  E --> F[SSRIs block serotonin reuptake]
  F --> G[More serotonin in synapse]
  G --> H[Receptor sensitivity changes 4-6 weeks]
  H --> I[Improved mood]

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How SSRIs Work at the Synapse

At the synapse, communication between neurons normally follows these steps:

1. An electrical impulse travels down the pre-synaptic neuron
2. Serotonin is released from vesicles into the synaptic gap
3. Serotonin binds to receptors on the post-synaptic neuron, passing the signal on
4. Serotonin is then either broken down or reabsorbed (reuptake) back into the pre-synaptic neuron

SSRIs work at step 4: they selectively block the serotonin reuptake transporter, leaving more serotonin in the synapse to continue activating post-synaptic receptors. Over several weeks, this increased activity is thought to promote neuroplastic changes — including changes in receptor sensitivity and growth of new synaptic connections — that underlie clinical improvement. This delay explains why symptom relief typically takes around 4–6 weeks even though serotonin levels change within hours.

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MAOIs — An Older Class of Antidepressants