In depression, the metabolism of neurotransmitters in the brain is out of balance. However, the exact neurochemical dysfunction of depression is not known. Antidepressants appear to increase the availability of the neurotransmitters serotonin and noradrenalin in the synaptic cleft in some parts of the brain. Recent preclinical studies show that antidepressants also consistently reduce the activity of neurons in the locus coeruleus in the brain stem where the noradrenergic neurons are located. Antidepressants also increase the availability of BDNF within the limbic system, a neurotrophin involved in neurogenesis and neuroplasticity.
Pharmacotherapy for depression should consist of acute therapy with antidepressants up until response or even remission is achieved (usually 4 – 6 weeks) and continuation therapy for a further six months to prevent relapse. Some patients will need maintenance therapy for a longer period of time. Rates of relapse are about twice as high when antidepressant medication is discontinued.
There are many different types of antidepressants, which differ more in terms of side effects than in efficacy. Two important groups of antidepressants are tricyclic antidepressants (TCA) and Selective Serotonin Reuptake Inhibitors (SSRIs). TCA include amitriptyline, clomipramine, dibenzepine, and doxepine, and side effects include delirium, dry mouth, and tremors. SSRI include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. When introducing antidepressants to the patient, it is important to inform them about possible side effects. It is also important to make clear that antidepressants do not change one's personality and are not addictive.
Other medications are sometimes necessary. If sedating drugs such as benzodiazepines are prescribed, it is important to limit the medication to a short time period (if possible less than 2 weeks) because of abuse and dependency risk; other drugs might be possible in psychotic depression (e.g. antipsychotics) or in treatment-resistant depression (lithium augmentation).