Discontinuing Medications

Almost all psychiatric medications, when suddenly stopped, can cause problems that either didn’t exist before or cause a relapse that would not have occurred had the medicines been stopped gradually. In fact, at least with lithium and probably a number of other medications as well, abrupt stoppage increases the number of people relapsing into their illnesses. It is always better to tapper medications over 4 weeks or more than to abruptly stop them. The longer a patient is on a medication, the more important and slower the withdrawal should be. I often suggest several months. Because of the withdrawal problem, it is important to watch your medication supply and fill your prescriptions ahead of time to assure you don’t run out.

Withdrawals Common with SSRIs, TCAs, MAOI, except Fluoxetine: A DB trial of 395 patients on fluoxetine with 60 switched to placebo for 6 weeks found no worsened or new symptoms of withdrawal, possibly due to the long half-life of the fluoxetine, a very long-acting SSRI. However, shorter acting SSRIs have been reported to have problems with abrupt discontinuation. David Michelson, J Clin Psychiatry 11/98 59:544-5. 35% paroxetine patients, 80% amitriptyline, 33% clomipramine and 32% phenelzine and 55% imipramine reported to have withdrawal. Symptoms are GI, headache, lethargy, sweating, sleep disturbance. Usually brief and mild and can be avoided by tapering. J Clin Psych 59:541

SSRI Withdrawal: Paroxetine Highest, Then Sertraline, Least Fluoxetine: Controlled study abrupt d/c 107 patients successfully treated for depression. Dizziness most common withdrawal symptom 57% parox & 42% sertraline. Paroxetine also nausea, weird dreams, fatigue, irritable, difficulty concentrating, aches, tense, chills, insomnia, agitation, diarrhea. Sertraline did have nausea and weird dreams. HAM-D increased with paroxetine. Brit J Psychiatry 00;176:363, Michelson. Withdrawal symptoms reported in less than 5% fluoxetine and as many as 86% fluvoxamine although fluvoxamine is usually less likely than shorter acting SSRIs, the latter was in a study of panic disorder patients. Symptoms can include hypomania, increased depression, agressiveness, and suicidality. Withdrawal symptoms can last up to 3 weeks and are sometimes helped by restarting the drug and tapering more gradually or using another anti-depressant with a similar profile. Zajecka J, et al: Discontinuation symptoms after treatment with serotonin reuptake inhibitors: a literature review. J Clin Psyc 97;58:291-7.

Paroxetine Withdrawal Marked But Not Fluoxetine, Citalopram or Sertraline: 85 pt in DB studies had DB 4-7 substitution of placebo for med. Only paroxetine patients suffered noticeable withdrawal effects: cognitive failures (P = 0.007), poorer quality of sleep (P = 0.016), and an increase in depressive symptoms, as rated both subjectively, using the Zung scale (P = 0.006) and by the clinician, using the Montgomery-Asberg Depression Rating Scale (P = 0.0003) and Clinical Global Impression (P = 0.0003). These cleared on restarting med. U Surrey. Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance. Hindmarch I, Kimber S, Cockle SM. Int Clin Psychopharmacol 2000 Nov;15(6):305-18

Withdrawal Reactions a Problem for Venlafaxine & Paroxetine: SSRIs are clearly associated with a higher risk of withdrawal syndrome (OR: 5.05) and in particular with venlafaxine and paroxetine (OR: 12.16 and OR: 8.47, respectively). The risk of withdrawal reactions appears to be greater with short half-life drugs such as paroxetine and venlafaxine. Reports of withdrawal syndrome with the use of SSRIs: a case/non-case study in the French Pharmacovigilance database. Trenque T, Piednoir D, Frances C, Millart H, Germain ML. Pharmacoepidemiol Drug Saf 2002 Jun;11(4):281-3; Half-life 5 hr with half-life of active metabolite O-desmethylvenlafaxine 11 hr. T-max of venlafaxine 2 hr and O-desmethyl 3 hr. With XR, these are 5 hr and 9 hr.

Olanzapine Withdrawal Psychosis = Supersensitivity Psychosis: 3 male schiz on 10-25mg/d for at least 8 months had sudden major relapses within 48 hours of adbruptly stopping olanzapine with mania, hyperactivity, grandeur, persecution, auditory hallus, insomnia. They responded to restarting olanzapine or another antipsychotic. Unlike classic withdrawal symptoms, no cholinergic symptoms and occurs sooner after drug cessation with sudden, often intense symptoms, sometimes with new symptoms. Llorca P-M, Vaiva G, Lancon C: Supersensitivity psychosis in patients with schizophrenia after sudden olanzapine withdrawal. Canad J Psyc 01;46:87-8

Gradual Withdrawal of Lithium Better: Withdrawal over 2-4 weeks lower relapse rate and longer relapse-free than rapid d/c <2 weeks. 161 patients stable bipolar on lithium > 1 yr. 77% d/c due to doing well and 22% due to pregnancy. Median time to recurrence 20 months gradual, 7 months abrupt. After 3 years, 37% graduals still no relapse. Baldessarini R, et al: Effects of the rate of discontinuing lithium meantenance treatment on bipolar disorders. J Clin Psyc 96;57:441-8, Harvard.

Switch Clozapine to Olanzapine Gradually: Switching patients abruptly from clozapine to olanzapine may result in schizophrenia relapses or clozapine withdrawal symptoms. Psyc Drug Alerts 3/97, pg 19