Treatment-resistant depression: what happens when antidepressants do not work?

Priya, a 32-year-old from Kerala, has been grappling with recurring bouts of depression that impeded her daily functioning. Despite medication for several weeks, her symptoms persisted. Seeking further guidance, she now undergoes repetitive transcranial magnetic stimulation (rTMS), a non-invasive procedure that employs magnetic pulses to target specific brain regions.

This scenario underscores the complexity of managing depression, according to experts. While antidepressants aid many, others experience continued symptoms despite treatment, necessitating doctors to reevaluate the diagnosis and consider alternative interventions. Depressive symptoms can encompass persistent sadness, diminished interest in activities, sleep disturbances, fatigue, cognitive difficulties, shifts in appetite, and can hinder one's capacity to work, maintain relationships, and manage everyday tasks.

Treatment-resistant depression is typically diagnosed when an individual has not responded satisfactorily to two or more distinct antidepressants, administered at suitable doses and durations, usually six to eight weeks each. Approximately 30% of those who have tried antidepressants may encounter treatment-resistant depression. The National Mental Health Survey of India reported a lifetime prevalence of depressive disorders among adults at 5.25% and the current prevalence at 2.68%.

However, it is the responsibility of medical professionals to ascertain whether the lack of improvement stems from treatment resistance or other factors. These could range from missed doses, insufficient dosage or duration, side effects, drug interactions, coexisting medical conditions, to alternative diagnoses such as bipolar disorder, which demands a distinct treatment approach.

Vivian Kapil, a consultant psychiatrist at SRM Prime Hospital, Chennai, emphasizes the necessity of ruling out substance use, psychotic symptoms, post-traumatic stress disorder, and other coexisting conditions. Underlying physical health issues, including anaemia and thyroid disorders, may also influence symptoms or complicate treatment.

When an antidepressant fails to offer sufficient relief, healthcare providers reassess the patient's response, medication adherence, dosage, treatment duration, and side effects before determining the subsequent course of action. If there is some improvement and the medication is well-tolerated, increasing the dosage may be contemplated.

If there is little or no improvement after a sufficient trial, doctors may switch to another antidepressant. Combining medications or incorporating psychotherapy, particularly cognitive behavioural therapy, are additional options. In specific cases, supplementary medications may be prescribed alongside an antidepressant. These determinations necessitate specialist oversight and appropriate monitoring.

Ketamine and esketamine may be contemplated in certain instances of treatment-resistant depression, especially when a more rapid response is desired. While some patients experience symptom improvement within hours or days, the response varies and may not be enduring. Potential adverse effects may include dizziness, nausea, elevated blood pressure, and temporary perceptual changes. These treatments necessitate medical supervision.

Electroconvulsive therapy (ECT) could be contemplated when depression is severe, other treatments have proven ineffective, or urgent intervention is required. This may be applicable when a person faces a high risk of suicide, exhibits symptoms such as dissociation, or is unable to consume adequate food or fluids. ECT is conducted under anaesthesia.

Some individuals may experience headaches, confusion for a brief period, or memory issues following the procedure. The severity of these effects can vary among individuals. A healthcare professional can assist in deciding whether ECT or an alternative treatment is appropriate, based on the person's symptoms, medical history, and past treatments.

Vasanth R., a consultant psychiatrist at Apollo Speciality Hospitals, OMR, Chennai, mentions repetitive transcranial magnetic stimulation (rTMS) as one of the newer treatment options in India. Its availability differs across centers, and the cost and requirement for multiple sessions may impact accessibility. rTMS involves repeated magnetic pulses to stimulate specific brain areas responsible for mood regulation.

Its suitability and potential benefits vary among patients and depend on their medical history and clinical assessment. Some individuals may require further treatment if symptoms resurface after an initial response. Unlike ECT, rTMS does not necessitate general anaesthesia, and the person remains awake during the procedure, which typically entails repeated outpatient sessions over several weeks.

Improvement may occur during treatment, but the duration and extent of improvement differ between individuals. Side effects may comprise scalp discomfort and headaches. Seizures are a rare but recognized risk. Before the treatment, doctors evaluate the person's medical history, including seizure risk and the presence of any implanted metal or electronic devices that could interfere with the procedure. rTMS and ECT differ in their methodologies, applications, and evidence of effectiveness.

Additional treatment options encompass vagus nerve stimulation (VNS), which employs electrical pulses to stimulate the vagus nerve. The selection of treatment, including the use of these approaches, hinges on each patient's clinical condition, past treatment response, and individual requirements.