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Changing Medications Usually Is Not Complicated, but Problems Can Arise

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Changing Medications Usually Is Not Complicated, but Problems Can Arise Changing medications usually is not complicated, but problems can arise— especially with shorter half-life agents Discontinuing an antidepressant? Tapering tips to ease distressing symptoms David J. Muzina, MD ost psychiatrists have encountered patients who report dis- Vice president and national practice leader tressing symptoms when they have forgotten to take their for neurosciences Medco Health Solutions Mantidepressant for a few days or during changes in the medi- Fort Worth, TX cation regimen. A discontinuation syndrome can occur with almost any antidepressant, highlighting the need to slowly taper these medi- cations when discontinuation is part of a treatment plan. This article discusses antidepressant discontinuation syndrome (ADS) in a patient who experienced substantial distress after a rapid anti- depressant taper in preparation for electroconvulsive therapy (ECT). My goal is to raise awareness of ADS, promote early detection of the syn- drome, and address proper prevention and management strategies. CASE REPORT Feeling ‘worse than ever’ Mr. J, a 32-year-old tax accountant, is hospitalized for a major depressive episode (MDE) associated with deteriorating function and suicidal ide- ation. This second lifetime MDE started 8 months before his admission to an inpatient mood disorders unit. Mr. J initially was treated with fluoxetine, up to 40 mg/d across 14 weeks, with good tolerability but no significant benefit. His psychiatrist switched Mr. J to bupropion but stopped it after 4 weeks because of side effects— including headaches, insomnia, and tremor—and limited antidepressant benefit. Venlafaxine XR was initiated next, at 150 mg/d within the first 2 ES ag weeks, increased to 225 mg/d at week 6, then titrated to 300 mg/d at week 10. After 10 weeks, aripiprazole, 5 mg/d, was added because Mr. J showed only partial, limited response to venlafaxine XR and this antipsychotic is ULT/GETTY IM A indicated for adjunctive treatment of major depressive disorder. M G A continued AD Current Psychiatry Vol. 9, No. 3 51 Table 1 because Mr. J was taking an “extended- release” medication. FINISH: Symptoms Within 72 hours, Mr. J went from tak- of antidepressant ing 300 mg/d of venlafaxine XR to none. discontinuation syndrome Within 2 days of cessation, he complained Flu-like symptoms of symptoms that could characterize a discontinuation syndrome. A potential Insomnia Antidepressant red herring in this case is that the patient discontinuation Nausea complained of feeling worse after his first Imbalance ECT treatment, and one might erroneously Sensory disturbances think the myalgias, headache, and other somatic symptoms were side effects of Hyperarousal (anxiety/agitation) ECT and/or anesthesia. Source: Reference 1 Typical ADS symptoms Clinical Point Nearly all antidepressant classes are as- SSRIs and SNRIs have Mr. J reported mild, transient restlessness sociated with ADS. Symptoms vary from but otherwise he tolerated the medications similar ADS symptoms patient to patient but typically include the well, and he claimed excellent adherence. “FINISH” syndrome: flu-like symptoms, but generally do After 6 additional weeks of treatment, how- insomnia, nausea, imbalance, sensory dis- not cause the ever, Mr. J was hospitalized because of per- turbances, and hyperarousal (anxiety/agi- anticholinergic effects sistent severely depressed mood, increasing tation) (Table 1).1 seen with tricyclic suicidal ideation, and inability to function Adverse effects after stopping tricyclic at work. antidepressants have been well document- discontinuation On admission, Mr. J is evaluated and agrees ed. They may include FINISH syndrome to ECT. To meet the ECT service’s protocol, features as well as cholinergic overdrive venlafaxine XR is reduced to 150 mg/d for 2 or “rebound” such as abdominal cramp- days and then stopped when ECT is started. ing and diarrhea.2-4 Reports of ADS after Aripiprazole is continued at 5 mg/d. patients stopped selective serotonin reup- Mr. J tolerates the first ECT treatment well, take inhibitors (SSRIs) emerged soon after but the morning before his second treatment these agents were introduced.5-7 Similarly, he complains of feeling “worse than ever.” An ADS has been reported with serotonin- agitated Mr. J reports dramatically intensified norepinephrine reuptake inhibitors (SNRIs), suicidal ideation—much more intrusive than including venlafaxine,8-10 venlafaxine XR,11 before he was hospitalized. He also com- and duloxetine.12 ADS symptoms are simi- plains of diffuse muscle aches and cramps, lar with SSRIs and SNRIs, generally without runny nose, nausea, headache, and burning the anticholinergic effects associated with sensations in both arms and hands. He with- tricyclic antidepressant discontinuation. draws consent for ECT and returns to the Fewer reports of discontinuation syn- mood disorders unit for ongoing treatment. drome exist for bupropion, mirtazapine, monoamine oxidase inhibitors (MAOIs), and nefazodone.13-17 Discontinuation-emergent ONLINE Could this be ADS? syndromes with these non-SSRI/non-SNRI ONLY Yes, it could. In this case, the inpatient psy- antidepressants tend to present differently. Discuss this article at chiatrist and treatment team were lulled With MAOIs, for example, neuropsychiatric http://CurrentPsychiatry. into a false sense of security by Mr. J’s his- symptoms such as severe anxiety, agitation, blogspot.com tory of few side effects with various treat- pressured speech, sleeplessness or drowsi- ments and medication changes. The ECT ness, hallucinations, delirium, and para- service wanted the patient off venlafaxine noid psychosis can be prominent.17 XR before beginning ECT, and the treat- ment team believed a quick taper would is unclear, and Current Psychiatry The prevalence of ADS 52 March 2010 not cause discontinuation symptoms published estimates vary widely because continued on page 58 continued from page 52 Table 2 ADS symptoms can range across a variety of system clusters System cluster Symptoms Neurosensory Vertigo, paresthesias, shock-like reactions, myalgias, numbness, sensitivity to sound, unusual visual sensations, ringing in the ears Neuromotor Tremor, myoclonus, ataxia/gait instability, visual changes, restless legs, Antidepressant problems with speech, tongue movements discontinuation Gastrointestinal Nausea, vomiting, cramps/bloating, diarrhea, anorexia Neuropsychiatric Anxiety/panic, depression, mood swings, suicidal ideation, irritability, impulsivity, confusion, psychosis Vasomotor Diaphoresis, flushing, temperature intolerance Other Headache, insomnia, vivid dreams, nightmares, lethargy/fatigue, flu-like symptoms ADS: antidepressant discontinuation syndrome Source: Construct suggested by Shelton,21 with additional symptoms added from other sources, including the discontinuation symptom checklist of Rosenbaum et al23 Clinical Point Evidence suggests shorter half-life of the lack of large controlled studies. highest risk for ADS, but other risk factors ADS rates with SSRIs/SNRIs have been remain presumptive (Table 3). antidepressants reported from as low as 0% for fluoxetine carry the highest to higher rates for shorter half-life anti- risk for ADS depressants: What causes ADS? • 2.2% with sertraline Although the exact cause of ADS is un- • 14% with fluvoxamine known, the literature proposes several • 20% with paroxetine theories. • 30.8% with clomipramine. Because of the central serotonin sys- These rates come from a retrospective tem’s complex connections, acute reduc- case note review of patients who discontin- tion in synaptic serotonin when an SSRI ued antidepressants under supervision.18 or SNRI is abruptly or too quickly stopped In a small cohort of outpatients being treat- may be the first in a cascade of steps affect- ed for major depressive disorder, stopping ing transmission of multiple monoamines. venlafaxine XR was associated with dis- Parallels have been drawn between the continuation symptoms for the next 3 days phenomenon observed with rapid deple- in 7 of 9 patients (78%), compared with 2 of tion of tryptophan—the essential amino 9 patients (22%) stopping placebo.11 acid precursor for the synthesis of 5-HT— and ADS seen with abrupt discontinuation Diagnostic criteria have been proposed of serotonergic antidepressants. This sug- for ADS associated with serotonin (5-HT) gests that acute drops in neurotransmitter reuptake inhibitors.19-22 Proposed ADS def- levels can precipitate neuropsychiatric and initions differ somewhat, but essentially 3 somatic manifestations of ADS.24 features guide the diagnosis: Patients’ uncomfortable symptoms likely • appearance of characteristic symptoms are caused by the serotonin, norepinephrine, (Table 2)21,23 and cholinergic systems and their complex • timing of those symptoms, which interactions.25 Individual genetic factors may usually emerge within 1 week of abrupt influence patients’ vulnerability for ADS. cessation or marked reduction of the anti- depressant • symptoms generally are mild, short- Managing ADS lived, self-limiting, and/or rapidly reversed Awareness and prevention. ADS can be by restarting the original antidepressant. misinterpreted as side effects of newly Evidence suggests shorter half-life anti- started treatment after an antidepressant is Current Psychiatry 58 March 2010 depressants may be associated with the stopped. In Mr. J’s case, the appearance of muscle aches, headaches, and other ADS Table 3 symptoms after ECT was started easily could have been perceived as adverse ef- Possible patient risk factors fects
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