Since the first antidepressant in the 1950s, biological treatments for mood disorders have largely focused on altering monoaminergic neurotransmission, with only partial success. In the landmark STAR*D trial, 1 out of 3 patients did not achieve remission with a 4-tiered monoaminergic treatment algorithm. Neuromodulation therapies take an alternate approach: directly altering the brain’s electrical activity through electro-magnetic stimulation.
Selecting an intervention
Neuromodulation can be divided into invasive and non-invasive methods (Table). Both are mainly indicated for depressive symptoms, generally as an adjunct to pharmacotherapy and psychotherapy and usually in patients with treatment resistance. Treatment resistance means lack of response to 2 to 4 medications with adequate dose and duration. Usually, resistance includes lack of response to multiple medication classes and evidence-based psychotherapy.
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That said, neuromodulation is not a panacea. A careful examination of a patients’ psychosocial structure is necessary, as their mood is unlikely to show lasting change if severe, persistent stressors are present. Similarly, comorbid personality disorder may contribute to depressive symptoms or alter the response to neuromodulation.
Electroconvulsive therapy (ECT). This hospital-based treatment uses an electrical current to induce a tonicclonic seizure under general anesthesia. An acute series consists of 3 weekly treatments for up to 4 weeks, with each session requiring at least an hour from pre-op to recovery.
ECT remains one of our most rapid and effective treatments for unipolar depression. Even with treatment resistance, response rates can exceed 70% to 80%. For those who respond but eventually have symptom relapse, maintenance ECT (weekly to monthly) is possible. ECT is safe and effective in bipolar, psychotic, and peripartum depression. In cases of depression with severe suicidal ideation, psychosis, or life-threatening catatonia, ECT should strongly be considered even in the absence of multiple medication trials.
While there are no absolute contraindications to ECT, increased intracranial pressure is a relative contraindication as treatment may exacerbate the condition. Cardiovascular disease also increases risk of treatment as the induced seizure causes a surge in blood pressure and heart rate. Patients’ primary concern, however, is the possibility of autobiographical memory loss. This is usually limited to memories from the treatment day, but patients (and some clinicians) still believe there is a risk of long-lasting cognitive impairment. Large studies and meta-analyses do not support these concerns. Moreover, cognitive risk is greatly reduced with modern techniques such as ultrabrief right unilateral ECT, which are just as effective as older approaches.
This highly effective treatment is often seen as a last resort, wasting months to years of patients’ lives on ineffective treatments. Discussing and delivering ECT earlier in the treatment algorithm would likely be beneficial. A challenge, however, is access. An acute ECT series is psychosocially disruptive, since patients usually are unable to work or to drive on treatment days. Hospitals find ECT difficult to justify financially, as it requires an anesthesiologist, additional support staff, and clinical space, all of which may be limited.
Focal electrically administered seizure therapy (FEAST) is a novel form of ECT that steers current away from the hippocampus, potentially reducing cognitive adverse effects. Pilot trials have been positive, and randomized trials should start in the next 1 to 2 years.1
Dr Wang is Psychiatry Resident, and Dr Widge is Assistant Professor, Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN. Dr Wang reports no conflicts of interest concerning the subject matter of this article; Dr Widge reports patent applications in the area of deep brain stimulation that are not licensed to any entity.
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