When Antidepressants Don’t Work: Exploring Alternatives

Depression, the most common mental disorder, remains the second leading cause of disability among adults, affecting over 8% of all US adults every year and seriously impairing their ability to live freely.

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The Star*D Trial was a nationwide study to find out the overall efficacy of antidepressants and psychotherapy for treatment of major depressive disorder. The study reported that one third of depression patients did not respond to the use of multiple antidepressants across different classes. Also, after the failure of the first antidepressant, the subsequent antidepressants showed much less response to the use of subsequent antidepressants.

Side effects of antidepressant medications:

The usual side effects of antidepressants are most common during the first few weeks of treatment (especially GI or anticholinergic side effects), This is typically followed by a decrease in severity or a complete disappearance of side effects over time. Common side effects may include nausea, diarrhea or constipation, fatigue, weight gain, sleep problems, reduced sex drive, anxiety or agitation. However, for some, the side effects of antidepressants may persist long-term, which can be extremely difficult to tolerate.

Pharmacogenetic evidence suggests that a significant number of individuals have a high intolerance to antidepressants. They may be predisposed to severe side effects from antidepressants because of specific genetic predispositions resulting in very slow removal of the drug from the body or specific changes at the receptor levels. They are likely to give up the use of medications after suffering from severe side effects.

Can antidepressants stop working?

It is frequently observed that antidepressants may work consistently for a while and then lose their effectiveness altogether. Depression results from complex interactions of genetics, life experiences, ongoing life stressors, medical illness and the changing brain and body mechanisms with age.  The medications which worked for some time may seem no longer effective under different set of conditions.

Treatment resistant depression (TRD):

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This term is often used to describe a lack of  therapeutic response from multiple psychiatric medications used by psychiatrists for treating the patient’s depression.  In context of lack of therapeutic response, most psychiatrists would make appropriate changes in treatment including increasing the dosage, change to different class of antidepressant (changing from SSRI to NSRI), or adding another antidepressant from a different class (adding Bupropion etc.), or augmenting the antidepressant response by adding low dose novel agents (antipsychotics). When all of these treatment approaches fail, including psychotherapy, then patients’ depression is often termed ‘treatment resistant’ to antidepressants. 

To stop or continue the use of antidepressant for TRD?

For some people with treatment-resistant depression, antidepressants may generally have little or no positive effect on one’s depression symptoms, which, combined with possible long-term undesirable side effects, may further worsen one’s mood and quality of life. Any changes in medications for TRD should be done carefully under the guidance of a psychiatrist.

TMS Therapy for treatment-resistant depression

Traditionally ‘psychotherapy and pharmacotherapy’ are considered the two major pillars of treating mental disorders. However, TMS (transcranial magnetic stimulation) is now considered the 3rd major pillar of psychiatric care since it was FDA approved in the US in 2008. It is a non-invasive, non-drug, outpatient brain stimulation therapy that uses short pulses of concentrated magnetic fields to those brain regions involved in depression and other psychiatric disorders.

TMS therapy for depression uses magnetic pulses to the left prefrontal cortex of your brain—the part responsible for mood regulation. Magnetic pulses produce very small electrical currents in the brain regions resulting in a number of local effects like: stimulating brain cells to release neurotransmitters, increasing blood flow, enhanced neuronal connectivity and neuroplasticity.

Just like an MRI scan, TMS therapy is generally a painless procedure. There are very few side effects, mainly scalp discomfort or mild headache in the first week.  There are no reported harmful side effects to the brain and there are no systemic side effects, as caused by medications. TMS patients can get right back to their daily routine with no impairment after a session.

While there is no cure for depression, TMS therapy is an extremely effective treatment for major depression when counseling and medication have both failed to yield positive results. The treatment response to TMS with recently improved protocols is over 70% in the majority of patients with depression.  

If you have been diagnosed with major depression or an anxiety disorder, have exhausted all other possible treatments (considered treatment resistant depression), then TMS may be the next best treatment option for you, if you meet the criteria for TMS therapy. Sleep TMS & Wellness Center in Great Neck offers state-of-the-art TMS therapy on Long Island. It is supervised by Dr. Gupta, a neuropsychiatrist who is quadruple board-certified with over 25 years of clinical experience. STW center has two TMS systems, with above average outcomes from use of neuro-navigation and an excellent TMS staff.

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