Improved Mood and Remission of Symptoms in Long-term Major Depression Using Vagus Nerve Stimulation

Amita R. Patel, MD, CMD, MHA, CPE; Shannon M. Wozniak, NP

Disclosures
In This Article

Case Report

J.F. is a 68-year-old married white woman with a 32-year history of treatment-resistant MDD. Her early treatment included ineffectual trials of tricyclic antidepressants, serotonin reuptake inhibitors, and dual-action antidepressants as well as adjunctive treatments with antipsychotic agents and anxiolytics. By November 1988, J.F. had been hospitalized 5 times. She was recommended for and received ECT. Although her suicidality initially remitted, she remained depressed and required further ECT in January 1989.

By the time she was referred to our office in September 1994, J.F had had MDD with chronic dysthymic symptoms, characterized by feelings of worthlessness, low self-esteem, and a daily lack of energy and motivation, for 20 years. During a major depressive episode in January 1995, she was treated aggressively with maximum doses of dual-action antidepressants in combination with serotonergic agents. She showed a partial response and was augmented with methylphenidate (Ritalin).

J.F.'s low-grade depressive symptoms did not fully remit. Over the next 10 years, she was prescribed alternative medications, which frequently were ineffective or caused unacceptable side effects. Her primary maintenance drug regimen consisted of high doses of venlafaxine hydrochloride (Effexor XR) (up to 375 mg SID), trazodone hydrochloride (Desyrel) 150 mg QHS, clonazepam (Klonopin) 0.5 mg TID, and Ritalin 20 mg TID. She had episodes of major depression for 3 to 6 months every year, during which doses were adjusted and alternative medications tried. During February 2001, ECT was again administered, but improvements in mood were transient and did not result in a meaningful decrease in antidepressant medications.

The patient's long course of treatment-resistant major depressive episodes made her a strong candidate for VNS therapy. She and her family were counseled and expressed a desire to proceed with the new treatment. In February 2006, J.F. underwent VNS therapy device implantation; stimulation was activated during an office visit later that month. At the time, J.F. was receiving Ritalin 20 mg TID, Klonopin 0.5 mg QID, bupropion (Wellbutrin SR) 100 mg TID, duloxetine hydrochloride (Cymbalta) 60 mg QAM, and zolpidem tartrate (Ambien CR) 12.5 mg QHS. Within 4 months, the patient noted substantial improvements in mood. By July 2006, the current had been titrated up to an output of 1.25 mA, standard signal frequency of 30 Hz, pulse width of 500 microseconds, and signal time of 30 seconds on and 5 minutes off.

Improvements in J.F.'s mood and quality of life were measured by physician observation, clinical signs and symptoms, changes in daily functioning, and the patient's own account. Twelve months since initiation of VNS therapy, J.F. seems to be in complete remission and she no longer meets criteria for major depression nor shows evidence of chronic dysthymic disorder. J.F. demonstrates a significant increase in energy and motivation without the use of stimulant medication, and she notes a higher activity level in her daily life and "around the house." At age 68, she describes a fullness of mood and energy levels not experienced since her mid-30s. In conversation she is more spontaneous and verbalizes her feelings better. Although voice alteration is the most commonly reported side effect with VNS therapy, J.F. has experienced no adverse events.

Perhaps the most significant improvement since device activation has been the reduction from 5 to 3 medications. The patient is now maintained on antidepressant monotherapy. Augmentation with Wellbutrin and Ritalin has been discontinued, which reduces her risk for serious cardiovascular side effects in light of her comorbid conditions. Frequency of Klonopin 0.5 mg has been reduced to 3 times a day. The patient had been experiencing frequent falls, but these have decreased in conjunction with the reduction in medication. The profound improvements experienced by J.F. appear to signal the utility of VNS therapy for major depression in older women with a longstanding history of treatment failure.

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