5.2 Treatment-resistant depression and somatic treatments
Switching between antidepressant medications is a common strategy for managing depression, but whether effectiveness can be improved remains controversial. ‘Treatment-resistance’ is said to occur where depression does not respond to (i.e. symptoms are not alleviated following) two or more trials with antidepressant medications. Combination therapies of antidepressant drugs can sometimes be effective (drugs that are recommended for treatment-resistant depression are aripiprazole, quetiapine fumarate and the combination of olanzapine with fluoxetine) (Kupfer et al., 2012). Two stage (augmentation and combination) approaches are based on the understanding that one treatment strategy alone is unlikely to treat the varied symptoms of depression and that switching to a different treatment is dependent on the individual’s response to the first approach and a reassessment.
Psychological therapies can be effective for mild to moderate depression, and although a combination of psychotherapy and medication may be more effective in reducing the chances of recurrence and relapse, this may still not be sufficient to address the symptoms in some cases of severe depression.
Nonpharmacological (somatic) treatments aimed at the underlying neurobiology for medication-resistant forms of severe depression include electroconvulsive therapy (ECT), brain stimulation techniques such as deep brain stimulation (DBS) and transcranial magnetic stimulation (rTMS). These procedures are believed to modulate the underlying neurotransmission affected in depression.
ECT is considered to be effective for treatment-resistant depression (with a 50-75% response in those who do not respond to antidepressant medication) (Bschor et al., 2014). Although usually transient (short-lived), side effects can include confusion, disorientation, and memory loss. DBS involves implanting electrodes, connected to a pulse generator, bilaterally within the brain. Electrical stimulation is believed to modulate neurotransmission in the cortico-striatal-thalamic-cortical circuit (including the cingulate gyrus, nucleus accumbens and ventral striatum,among other areas). Although deep brain stimulation is still in early stages of investigation and shows promise for treatment-resistant depression, it is not currently approved in the US or in Europe. rTMS has been approved in the US for the treatment of major depressive disorder (for those who have not responded to a course of an antidepressant drug). The procedure involves producing a magnetic field around target areas of the brain – the left and right dorsolateral prefrontal cortex – in depression (Kupfer et al., 2012).