5.1.4 - Treatments for unipolar depression

How SSRIs affect the synapse

Selective serotonin reuptake inhibitors, or SSRIs, are a biological treatment that alters serotonin signalling.

A neuron releases serotonin into the synaptic cleft, the gap between neurons. Serotonin can bind to receptors on a receiving neuron. Normally, transporter proteins on the releasing neuron take some serotonin back into that neuron; this is reuptake, one process that limits the signal. An SSRI inhibits the serotonin transporter, reducing reuptake so serotonin remains available in the cleft for longer. It does not supply serotonin as a replacement chemical or block the receiving neuron's serotonin receptors. “Selective” refers to its stronger action on serotonin reuptake relative to other monoamine transporters, not an absence of every other effect.

Sertraline and fluoxetine are examples. This immediate pharmacological action is established, but the complete pathway from altered signalling to improvement in mood is more complex. Changes in receptor regulation and neural processing over time can contribute. Clinical benefit usually develops gradually over weeks, rather than occurring as soon as the first dose affects a transporter. Some people improve substantially, some partially and some little.

It is tempting to reason that if an SSRI helps, the person must originally have had a serotonin deficiency. That reverses the inference. A treatment can change a process and help without demonstrating that the disorder began because that process was deficient. SSRI effectiveness is compatible with serotonin contributing to treatment, while depression can involve multiple biological, cognitive and environmental factors. NHS antidepressant information.

Medication benefit and informed choice

An effective treatment improves meaningful outcomes enough to justify its burdens and risks.

Randomised comparisons with placebo can test whether medication offers benefit beyond expectation, clinical contact and changes that would have occurred anyway. In DeRubeis and colleagues' 2005 trial of adults with moderate to severe major depression, response at eight weeks was 50% in the medication condition and 25% with pill placebo. The medication regimen began with paroxetine, an SSRI, but allowed augmentation where needed. The finding supports that treatment regimen; it is not an isolated test showing every SSRI has the same effect. Original trial abstract.

Response means a defined degree of improvement; remission means symptoms have reduced below a specified threshold. Neither automatically means permanent recovery. A study must specify its definition and follow-up. Random assignment supports causal comparison by reducing pre-existing group differences, but outcomes in research clinics may not exactly match ordinary services, different severity groups or people with different additional difficulties.

SSRIs can cause nausea, sleep disturbance, headaches or sexual difficulties. Some adverse effects ease, while others persist. Monitoring matters because a person may experience adverse effects before improvement. Withdrawal symptoms can occur when medication is stopped or reduced; they are not identical to relapse and do not by themselves mean addiction. Changes in medication are managed with the prescribing professional rather than treated as an abrupt classroom experiment. NHS treatment information.

Informed consent requires understandable information about likely benefits, side effects, uncertainty and alternatives. Prescribing cannot be justified solely because pills are convenient for a service. NICE advises against routinely offering antidepressants first for less severe depression unless that is the person's informed preference; for more severe depression, several first-line options include medication and combined treatment. Severity, previous response, practical access and preference guide a shared choice. This current guidance illustrates individualised care rather than prescribing a treatment for an imaginary exam patient. NICE NG222, sections 1.5–1.6.

How CBT changes a maintenance cycle

CBT is a psychological treatment that changes interactions among thoughts, emotions and behaviour which can sustain depression.