45 - Time course

Time course

374 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 3 Time course The onset and severity of symptoms are related to the half-­life of the antidepressant. Placebo/nocebo effects and loss of therapeutic efficacy may also be important. Short half-­life antidepressants like paroxetine and venlafaxine produce symptoms within a day or two, whereas symptoms with fluoxetine can be delayed by 2–6 weeks.2 Symptoms can vary in duration, form and intensity and occur in any combination. While they can be mild and self-­limiting, there is substantial variation between individuals and, for some people, symptoms can last much longer than previously reported.6 The perception of symptom severity is probably made worse by the absence of forewarnings. Some symptoms are more likely with individual drugs (see below). Symptoms can be quantified using the Discontinuation–Emergent Signs and Symptoms Scale.7 Box 3.1  Factors influencing the incidence and severity of antidepressant withdrawal symptoms Pharmacological factors: ■ ■Pharmacokinetics ■ ■Drug half-life ■ ■Pharmacodynamics ■ ■Receptor affinities Treatment factors: ■ ■Duration of treatment ■ ■Dose ■ ■Method of tapering Patient-­specific factors: ■ ■Prior experience and anticipation effects Other factors: ■ ■Drug half-­lives – correlate with the severity and onset of symptoms. Symptoms typically more  severe with shorter half-­life drugs (e.g. ­venlafaxine, paroxetine) ■ ■Other pharmacokinetic factors: non-­linear pharmacokinetics ■ ■Receptor affinities: higher affinity for the serotonin transporter may confer higher risk of withdrawal symptoms (Continued) Table 3.8  Symptoms reported with other (non-­SSRI) antidepressants. Antidepressant type Symptoms Agomelatine Seems to be associated with a very low, if any, risk of discontinuation symptoms1 Bupropion Uncommon, but case reports have described anxiety, headache, insomnia, irritability and myalgias;8,9 single case report of acute dystonia10 Monoamine oxidase inhibitors* Common: agitation, irritability, ataxia, movement disorders, insomnia, somnolence, vivid dreams, cognitive impairment, slowed speech, pressured speech. Occasionally, hallucinations, paranoid delusions. RIMAs: flu-­like symptoms reported with moclobemide.11 NaSSAs (e.g. mirtazapine) Panic, anxiety, restlessness, irritability, hypomania, insomnia, dizziness, paraesthesia, nausea, vomiting10