Withdrawal from SSRIs

The SSRI medications, such as Prozac, Paxil, Zoloft, and Lexapro, and the SRIs, such as Effexor, almost always produce withdrawal symptoms (see chapter 6). These often severe symptoms were ignored for years and even today are too often ignored by a psychiatric community bent on blaming the patient s suffering on so-called mental illness. 

Consistent with my own clinical experience, Pasadena, California, psychiatrist Stuart Shipko (2002) listed the following major categories of SRI withdrawal symptoms  

electric, shocklike sensations, mostly commonly in the head, neck, and shoulders (zaps) 

a severe depressive syndrome with characteristic easy crying, different in quality from any depression prior to taking the SRI 

new onset of intense somatic and mental anxiety lasting minutes to hours not present prior to taking the SRI 

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Increased interest by EU in describing withdrawal from SSRIs... 

The reason for this warning is that abrupt cessation of SSRIs produces withdrawal symptoms in about 20 per cent of patients. Symptoms of withdrawal from antidepressant medication include gastrointestinal disturbances (abdominal cramping and pain, diarrhoea, nausea and vomiting), flu-like symptoms, headaches, sleep disturbances, dizziness, blurred vision, numbness, electric-shock sensations, twitches and tremors. Abrupt withdrawal can also produce symptoms of depression and anxiety, which can occur within hours of the first missed dose of the drug.11 Withdrawal symptoms are sometimes mistaken for a relapse, leading patients to resume antidepressant medication and to conclude that they need it in order to remain free of depression. Technically, this is not considered addiction , but it does seem awfully close. 

RBD is characterized by a relative absence of the atonia characteristic of REM sleep. This lack of atonia permits the physical acting out of dream mentation, particularly dreams involving confrontation, aggression and violence. RBD is seen most frequently in older men. RBD occurs in both acute and chronic forms. Acute RBD can occur during withdrawal from alcohol or sedative-hypnotics. RBD has also been induced by the tricyclics, SSRIs and venlafaxine. The chronic form of RBD may occur as part of an identifiable underlying neurological disorder, but typically is idiopathic. RBD may also be an initial manifestation of parkinsonism. RBD is very responsive to clonazepam, although this use has not been FDA approved. 

With respect to a specific and common clinical problem, advice to withdraw hypnotic medication should follow a careful evaluation of self-reported sleep patterns, psychological factors and psychosocial status. Ambulant monitoring can be helpful in patients who have encountered severe problems in effecting withdrawal. A careful psychiatric assessment should be made to ascertain whether the patient has clinically significant anxiety and/or depression. Both should be treated with a selective serotonin receptor inhibitor (SSRI) before withdrawal from the hypnotic is attempted. An optimal tapering schedule should be discussed with the patient some will attempt a rapid withdrawal over less than 8 weeks and others will require much longer. This is particularly so if previous attempts to withdraw have been unsuccessful. Carers, family and friends should be mobilized to help in withdrawal, should the patient wish this. Substitution of zolpidem may facilitate withdrawal but should be kept as a reserve strategy. 

Chapter 15 discusses SSRI withdrawal symptoms in more detail and describes how to successfully withdraw from psychiatric medications. 

Withdrawal symptoms from SSRIs can be very severe and lasting. In a few cases in my clinical practice, patients have chosen to remain on very low doses for sustained periods of time because they were unable to... 

Paroxetine at low concentration is dependent on CYP 2D6 for its clearance. However, this enzyme is almost completely saturated by paroxetine at low concentrations, which accounts for the nonlinear pharmacokinetics of paroxetine and why its half-life goes from 10 to 20 hours when the dose is advanced from 10 to 20 mg per day. At higher concentrations, paroxetine is most likely dependent on CYP 3A3/4 for its clearance. This dose-dependent change in the clearance of paroxetine probably accounts for the higher incidence of withdrawal reactions with this SSRI than might otherwise be expected for a drug with a half-life of 20 hours at steady-state on 20 mg per day (296, 297). 

In my clinical experience, many, and probably most, patients taking SSRIs suffer from drug-induced sexual dysfunction due to suppressed sexual appetite, inhibited sexual function, and emotional withdrawal, but the SSRIs often make them too apathetic or disinterested to complain to their doctors. They are too medication spellbound to care about their sexual and love life or the effects on their loved ones and partners. 

Psychiatry has yet to face the fact that it has trapped millions of patients into taking SSRI and SRI drugs for years on end because they are unable to endure the withdrawal symptoms. Sometimes the brain changes are so persistent or irreversible that the individuals feel compelled to remain on the drugs indefinitely. Often the withdrawal symptoms lead them mistakenly to believe that they suffer from an underlying mental illness that requires medication, when instead they have persistent brain dysfunction caused by medication. 

This infant s symptoms were similar to those described in other neonates whose mothers took SSRIs shortly before delivery, although in this case a contributory effect from olanzapine was also possible. The authors made the point that it can be difficult to decide from the clinical presentation whether neonatal problems, such as those described above, represent SSRI withdrawal (5HT deficiency) or SSRI toxicity (5HT excess). The fact that no paroxetine was detected in the infant s plasma led them to conclude that SSRI withdrawal was responsible for the symptoms in this case. 

Of 93 cases of neonatal symptoms associated with the use of SSRIs in mothers around the time of delivery 64 were associated with paroxetine but reactions were also reported in infants whose mothers had taken citalopram, fluoxetine, and sertraline (87). It is unclear from these data whether paroxetine is actually most likely to provoke the neonatal syndrome, but in adults its use is associated with more severe withdrawal reactions than other SSRIs. It should also be noted that it is not clear whether the syndrome described in neonates is due to SSRI withdrawal or a form of serotonin toxicity. 

Withdrawal symptoms in the 2 weeks after sudden discontinuation of citalopram have been examined in a double-blind, placebo-controlled study (24). Withdrawal symptoms were overall mild, but neurological and psychiatric disturbances were 2-3 times as common in patients randomized to placebo than in those randomized to continue with citalopram. The authors pointed out that withdrawal symptoms were particularly common in patients who were randomized to placebo who also had depressive relapses. This shows the difficulty of disentangling the effects of depressive relapse from those of pure treatment withdrawal. However, it is also possible that acute withdrawal of medication induces an abnormal neu-robiological state, in which both depression and abstinence symptoms are more likely to occur. It would be wise to warn patients about the possible effects of missing doses of the shorter-acting SSRIs. 

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