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Exploring depression
Exploring depression

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5.1 Pharmacological and psychological therapies

Pharmacotherapy with antidepressant medications (see Table 2) and depression-specific psychological therapies (see Box 11) can be effective treatments for depression, either delivered as monotherapy or in combination (Kupfer et al., 2012). Cognitive behavioural therapy (CBT) is empirically supported for mild to moderate depression, and interpersonal psychotherapy can be as effective as CBT in some cases. For those who have had three or more previous depressive episodes, mindfulness-based cognitive therapy has an additive effect. Problem-solving therapy has also been shown to be effective in treating depression. Computer and internet-based therapies are also being developed.

Table 2. Antidepressant medications used in the treatment of depression (adapted from Kupfer et al., 2012)
Class of Drug Examples Proposed mechanism of action
Selective serotonin reuptake inhibitors (SSRIs) Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline Selectively inhibit the reuptake of serotonin
Tricyclic antidepressants Amitriptyline, Desipramine, Doxepin, Imipramine, Maprotiline, Nortriptyline, Protriptyline, Trimipramine Nonselectively inhibit the reuptake of monoamines, including serotonin, dopamineand noradrenaline
Noradrenaline-dopamine reuptake inhibitor Bupropion Inhibits the uptake of noradrenaline and dopamine
Serotonin modulator Nefazodone, Trazodone Primarily antagonises 5-HT2 receptors
Serotonin-noradrenaline reuptake inhibitors Desvenlafaxine, Duloxetine, Venlafaxine Inhibits the reuptake of serotonin and noradrenaline
Noradrenergic and specific serotonergic modulator Mirtazapine Primarily antagonises alpha-2 and 5-HT2C receptors
Serotonin reuptake inhibitor and 5-HT1A receptor partial agonist Vilazodone Potently and selectively inhibits serotonin reuptake and acts as a partial agonist at 5-HT1A receptors
MAO inhibitors Isocarboxazid, Phenylzine, Tranylcypromine, Selegiline Nonselectively inhibits enzymes (MAO-A and MAO-B) involved in the breakdown of monoamines, including serotonin, dopamineand noradrenaline


MAO: monoamine oxidase; 5-HT: serotonin (5-hydroxytryptamine).


Ketamine, an NMDA receptor antagonist and analgesic/anaesthetic drug, has more recently been investigated as a new form of treatment for severe depression. At the time of writing, a derivative of ketamine (esketamine, marketed as the nasal spray ‘Spravato’) has subsequently been approved by the Food and Drug Administration (FDA) in 2019, for the treatment of severe depression in the United States. Heralded as the first ‘new’ pharmacological treatment for depression in over thirty years, it will be offered to patients who have tried at least two other treatments without success, and will be administered under medical supervision and monitoring, due to its potential for abuse (FDA 2019).

Box 11 Psychological therapies for depression

Cognitive-Behavioural Therapy (CBT)

CBTcan help to change negative thinking, to interpret the environment and interactions in a positive way, to recognise factors that may be contributing to the depression and to help change behaviours that may be making the depression worse. Longitudinal formulations such as the 5 ‘Ps’ (predisposing factors, precipitating factors, presenting difficulty, perpetuating factors, protective factors) can be useful.

Interpersonal Therapy (IPT)

IPT is designed to help an individual understand and work through troubled relationships that may cause the depression or make it worse, by exploring major issues that may add to depression, such as grief, or times of upheaval or transition.

Problem-Solving Therapy (PST)

PST can improve an individual’s ability to cope with stressful life experiences, and can be an effective treatment option particularly for older adults with depression. Using a step-by-step process, the individual identifies problems and comes up with pragmatic (realistic) solutions. Typically a ‘short-term’ therapy, PST may be conducted in an individual or group format.