P2.PS.4Interventions for depression: antidepressants (SSRIs) and CBT — how they work and effectiveness

Two evidence-based treatments dominate UK depression care: antidepressant drugs, especially SSRIs, and Cognitive Behavioural Therapy (CBT). NICE guidelines often recommend either, or a combination, depending on severity.

SSRIs (Selective Serotonin Reuptake Inhibitors)

Examples: fluoxetine (Prozac), sertraline, citalopram, escitalopram.

How they work (links to P2.B.2):

1. After a presynaptic neuron fires, serotonin is released into the synapse and binds receptors on the postsynaptic neuron.
2. Normally, the presynaptic neuron then reuptakes the serotonin to recycle it.
3. SSRIs block the reuptake transporter — serotonin stays in the synapse longer, prolonging postsynaptic stimulation.
4. Over weeks, downstream effects (neuroplasticity, neurogenesis in the hippocampus) drive symptom improvement.

Strengths:

• Wide evidence base (Kirsch & Sapirstein 1998 meta-analysis showed efficacy over placebo, especially for moderate-to-severe depression).
• Easy to administer; relatively cheap.
• Useful when severe depression makes therapy hard to engage with.

Weaknesses:

• Side effects: nausea, headache, sexual dysfunction, weight change. Discontinuation symptoms if stopped abruptly.
• Delayed effect: 4–6 weeks before full benefit; risk of suicide may briefly rise in young people in early weeks.
• Tackles symptoms not causes: relapse common after discontinuation.
• Effect size debated: Kirsch (2008) argued SSRIs offer little advantage over placebo for mild depression.
• Long-term effects less well studied.

Cognitive Behavioural Therapy (CBT)

Developed from Beck's cognitive theory (P2.PS.3). The therapist works with the client to:

• Identify negative automatic thoughts and underlying schemas.
• Challenge them — examining evidence for and against; testing alternative interpretations.
• Replace distortions with more balanced thinking.
• Pair with behavioural experiments — scheduling activities that disconfirm depressive predictions ("if I go to the gym I'll feel worse" → tested → contradicted).

Typical course: 12–20 weekly sessions, structured agenda, homework between sessions.

Strengths:

• Effects often outlast treatment — CBT changes thinking habits and reduces relapse compared with medication alone (Hollon et al., 2005).
• Evidence base from many RCTs; recommended by NICE.
• Empowers the client; addresses causes not just symptoms.
• Avoids drug side effects.
• Available digitally (computerised CBT) for mild-to-moderate cases.

Weaknesses:

• Requires effort, motivation and verbal/cognitive skills — can be hard for severely depressed clients to engage.
• Time-intensive (12+ sessions); waiting lists in NHS.
• Less effective for severe or psychotic depression as a sole treatment.
• Therapist quality varies.

SSRIs vs CBT — when to use which?

NICE-style guidance:

• Mild depression: psychological interventions first (CBT, behavioural activation). Drugs not usually first-line.
• Moderate depression: CBT or SSRI; combination if severe or persistent.
• Severe depression: usually combination of SSRI + CBT; possibly inpatient care.

Combination is usually more effective than either alone, especially long-term.