Utsättningssymtom av venlafaxin

Fråga: Jag har en patient som haft venlafaxin under flera år och nu har vi trappat ut läkemedlet pga utebliven effekt. Under egentligen hela nedtrappningen (som skett inneliggande på sjukhus) har patienten haft huvudvärk, yrsel, illamående och ”stötar igenom kroppen”, vilket tolkats som utsättningssymptom. Nu är venlafaxin utsatt helt sedan en vecka men symptomen finns kvar. Jag undrar vad senaste forskningen säger om venlafaxins nedtrappning, utsättningssymptom och eventuell behandling av dessa?

Svar:
Sammanfattning

The rates of withdrawal symptoms from both RCT and open trials range from 23 to 78% after discontinuation of venlafaxine.
According to FASS the risk of withdrawal symptoms may be dependent on several factors, including the duration and dose of therapy and the rate of dose reduction [1]. Published studies and case reports we find show no clrear correlation between significant withdrawal from venlafaxine and dosage [2], indication for use, length of treatment [3], or taper duration [4].

The most frequently reported adverse symptoms of tapering or stopping venlafaxine are nausea, vertigo, irritability, and lethargy, though more distressing symptoms have been reported, including visual disturbances, unpleasant physical sensations, motor and coordination problems, cataplexy, delirium, mania, and psychosis. Aside from causing significant distress, these symptoms may be mistaken for other illnesses, lead to unnecessary tests and treatment, and potentially force patients to continue a medication that could otherwise have been discontinued.

The management methods of withdrawal in venlafaxine-treated patients are described only in case reports and include reintroduction of venlafaxine, introduction of fluoxetine, chlorpromazine, ondansetron, sertraline, a low dosage of lorazepam, a combination of lorazepam and valproate, and duloxetine.

Svar

The rates of withdrawal symptoms from both RCT and open trials range from 23 to 78% after discontinuation of venlafaxine.
Withdrawal symptoms include a wide range of clinical manifestations, regardless of whether gradual or abrupt discontinuations has been implemented, and they are similar to those observed after discontinuation of SSRI [5]. They typically occur within a few days from drug discontinuation and last a few weeks. However, episodes of a longer duration have been reported, suggesting the presence of persistent postwithdrawal disorders [6]. Few studies reported data about rebound of symptoms [7].

Withdrawal Symptoms in Double-Blind RCT

Single Drug and Placebo Comparisons

Two studies that were concerned with the use of venlafaxine [8, 9] reported a significantly greater incidence of withdrawal in venlafaxine-treated patients compared to placebo. Symptoms commonly associated with discontinuation were headache, dizziness, nausea, lightheadedness, excessive sweating, irritability, dysphoria, and insomnia.

Single Drug at Different Doses and Placebo Comparisons

Allgulander et al. [10] calculated a significantly higher incidence of discontinuation symptoms after extended-release (ER) venlafaxine at any dosage (52% with 37.5 mg/day, 35% with 75 mg/day, and 78% with 150 mg/day) compared to placebo (~12%). It was highest after abrupt discontinuation of 150 mg/day ER venlafaxine.

Multiple Drugs and Placebo Comparisons

Hartford et al. [11] detected significant differences between venlafaxine (75–225 mg/day) and placebo but not between duloxetine (60–120 mg/day) and placebo in terms of rates of withdrawal symptoms. Nausea and dizziness were the most frequently reported symptoms.

Multiple Drug Comparisons

Montgomery et al. [12] found significantly higher withdrawal scores in the venlafaxine group than in the escitalopram group. Unsteady gait, burning, forgetfulness, shaking, restless feeling, nausea, confusion, sweating, agitation, fatigue, and dizziness were significantly greater in the venlafaxine group.

Sir et al. [13] were unable to detect significant differences between venlafaxine and sertraline, except for tremor, vertigo, and impaired coordination, which were more than twice as common in the venlafaxine group.

Withdrawal Symptoms in Open Trials and Naturalistic Prospective/Retrospective Studies

Most venlafaxine-treated patients experienced discontinuation symptoms, with rates around 75% [7, 14]. In the report by Dallal and Chouinard [7], patients developed both withdrawal and rebound symptoms, including anxiety, agitation, tremors, vertigo, headache, nausea, tachycardia, tinnitus, and akathisia. In the investigation by Cohen et al. [14], the most commonly reported discontinuation symptoms were headache, vivid dreams or nightmares, sweating, muscle cramps, and trouble sleeping.

Tint et al. [4] conducted an open randomized naturalistic prospective study to evaluate whether a short or a longer taper influences the incidence of discontinuation symptoms. Patients treated with fluoxetine, paroxetine, citalopram, fluvoxamine, or venlafaxine for at least 6 weeks were randomized to a 3-day or a 14-day taper period before starting a new antidepressant treatment. Overall, a significant increase in withdrawal symptoms was observed 5–7 days after tapering, without significant differences between the 2 discontinuation methods.

Baboolal [15] retrospectively reviewed the case notes of 68 patients treated with venlafaxine XR at 37.5–75 mg/day. The most common discontinuation symptoms were dizziness, nausea, and headache. Other reported symptoms were fatigue, tremor, vomiting, shock-like sensations in the body, diarrhea, bizarre dreams, inability to walk unaided, insomnia, a “bad feeling,” sweating, lightheadedness, fear of “going crazy,” a crawling sensation on the scalp, fear, and depersonalization. These symptoms were associated with significant impairment in social and occupational functioning in all of the patients.

Withdrawal Symptoms in Case Reports

There are few published case reports of withdrawal symptoms in adult patients (aged 24–76 years) taking venlafaxine [48-66]. Discontinuation symptoms were reported independently of the treatment duration (from few weeks to years) and discontinuation (abrupt vs. tapered). Symptoms usually appeared within a period of 24–48 h after discontinuation. Venlafaxine withdrawal symptoms generally waned within a period of 3 weeks. However, there were few cases in which these symptoms lasted for months or even years [16]. In 1 case did symptoms spontaneously remit in 4 days [17]. Venlafaxine was generally reintroduced to address these symptoms. Other management methods included fluoxetine [18, 19], ondansetron[20], sertraline [21], a low dosage of lorazepam [22], a combination of lorazepam and valproate [23], and duloxetine [24, 25].

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