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SSRI discontinuation syndrome

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SSRI Discontinuation Syndrome also known as SSRI Withdrawal Syndrome or SSRI Cessation Syndrome, is a condition that can occur following the interruption or discontinuation of regular SSRI or SNRI usage (as well as many other types of Central Nervous System drugs, such as tricyclic antidepressants and MAOIs). The condition can begin between 24 hours to one week after discontinuation, depending on the half-life of the drug. Occasionally with Prozac, symptoms can take a fortnight or more to emerge, owing to the drug's extremely long half-life.

SSRIs are not addictive in the conventional medical use of the word (i.e. animals given free access to the drug do not actively seek it out and do not seek to increase the dose), but suddenly discontinuing their use is known to produce both somatic and psychological withdrawal symptoms, as described by researchers.[1] Compared to the withdrawal symptoms of such drugs as opiates, alcohol, or cocaine, these reactions are quite different and frequently less significant, although the prescribing labels acknowledge the possibility of "intolerable" discontinuation reactions and some patients are never able to completely withdraw from SSRI drugs.

Double-blind controlled studies now indicate that 35-78% of patients who, after five weeks or more of treatment with the medication, abruptly stop certain antidepressants or titrate down in 10mg increments or more, will develop one or more of the discontinuation symptoms. When allowed to run its course, the syndrome duration is variable (usually one to several weeks) and ranges from mild-moderate intensity in most patients, to extremely distressing in a smaller number.

Abrupt cessation of treatment with dopamine antagonists may precipitate a florid psychosis with delusions, hallucinations, and suicidal and/or homicidal behavior. It is better to slowly taper the dose (by 10% increments of the original dose) while closely observing the patient for exacerbation of psychotic symptoms.

Symptoms

A number of possible symptoms can characterize SSRI discontinuation syndrome. They can include:

The indicators of SSRI discontinuation syndrome are the following:

  • Interruption, cessation, or reduction of dosage in an SSRI treatment that has lasted four or more weeks.
  • Symptoms interfere with normal social, occupational, or other functioning.
  • Symptoms are not due to another medical condition, drug use, or discontinuation.
  • Symptoms are not due to a relapse of the condition for which the SSRI was originally prescribed.

Mechanism

Antidepressant withdrawal effects do not indicate addiction in the strict medical sense, but are rather the results of the brain attempting to reach neurochemical stability after an abrupt change. These can often be minimized or avoided by tapering off of the medication over a period of weeks or months, although this is not always successful, especially for long-term users.

Prevention and treatment

Patients should be advised of the elimination half-life times on their specific medication, and patients should be aware if changing from a long half-life medication such as Prozac, to a shorter one, that taking their dose regularly becomes much more important.

The condition may be avoided by either recommencing the original and or lesser dose of the SSRI, or slowly reducing (titrating) the dosage over several weeks or months. While slowly reducing the dosage does not guarantee that a patient will not experience the discontinuation syndrome, it is considered a safer method than abrupt discontinuation.

Treatment is dependent on the severity of the discontinuation reaction and whether or not further antidepressant treatment is warranted. In cases where further antidepressant treatment is required then the only step required is restarting the antidepressant; this is usually the case following patient noncompliance with the drug. If antidepressants are no longer required, treatment depends on symptom severity. Mild reactions may only require reassurance. Moderate cases may require symptom management, for example benzodiazepines can be used for insomnia. If symptoms are severe, or do not respond to symptom management (i.e., lifetime dependency has been induced by the antidepressent), the antidepressant can be reinstated and then withdrawn more cautiously.[2]

Persisting adverse effects

Some patients, especially those who have used the medicines for a long period of time or at a higher dosage, can experience persistent adverse effects on discontinuing an SSRI, which last well beyond the initial period of discontinuation syndrome. These can vary from mild (poor short-term memory, poor concentration, tinnitus) to more severe (akathesia, tachycardia, depersonalization, sexual dysfunction, extreme anxiety in excess of pre-treatment levels). Little research has been done into this phenomenon, so no reliable scientific analysis is available. If the patient is unwilling to recommence SSRI treatment, the problems can be mimimised to some extent with symptom management. Most patients complaining of persisting post-SSRI effects experience significant improvement within two years, although some symptoms have been known to persist indefinitely.

Discontinuation of Venlafaxine

Sudden discontinuation of venlafaxine has a high risk of causing potentially severe withdrawal symptoms.[3] The high risk of withdrawal symptoms may reflect venlafaxine's short half-life.[2] Missing even a single dose can induce discontinuation effects in some patients.[4] Discontinuations have a tendency to be significantly stronger than the withdrawal effects of other antidepressants including the tricyclic antidepressants, but are similar in nature to those of SSRIs such as Paroxetine (Paxil® or Seroxat®).

Symptoms of discontinuation are similar to other antidepressants including irritability, restlessness, headache, nausea, fatigue, excessive sweating, dysphoria, tremor, vertigo, irregularities in blood pressure, dizziness, visual and auditory hallucinations, feelings of abdominal distension, and paresthesia. Other non-specific mental symptoms may include impaired concentration, bizarre dreams, delirium, cataplexy, agitation, and worsening of depressive symptoms.[3][2][4][5][6][7][8] One symptom may include a feeling of spinning, similar to drunken "bed spins"; patients may experience spinning in two different directions, often felt between the area of the head above the nose and below the nose. This feeling of spinning is associated with severe nausea and disorientation. Electric shock sensations have also been reported[4][7] with patients describing the symptoms as "brain shivers". It has been suggested the sensations may represent an alteration of neuronal activity in the central nervous system.[9]

Studies by Wyeth-Ayerst and others have reported occasional cases of withdrawal symptoms severe enough to require permanent use.[citation needed] In some of these cases, successful discontinuation was eventually achieved by the addition of fluoxetine, which was later discontinued itself without difficulty.

Controversy

Venlafaxine has, along with the general group of SSRI and SNRI anti-depressants, been the subject of controversy as to efficacy and safety.

A petition to Wyeth, signed by more than 11,000 patients as of June 2006, argues that disclosure regarding the side effects and efficacy is neither full nor accurate and asks Wyeth to improve the Effexor documentation for patients and medical professionals.[1] The petition contains anecdotal comments regarding effexor's severe side effects, severe withdrawal difficulties, and that these effects were not communicated to them by their physicians. One psychiatrist posted her comments on the petition indicating that the training provided by Wyeth to practictioners did not adequately explain side effects or the severity of discontinuation. It is important for patients to be aware of these risks so their choice to take this drug is balanced against the severity of potential side effects

One early and controversial critic of antidepressants, Peter Breggin, a physician who opposes the overuse of prescription medications to treat patients for mental health issues, predicted iatrogenic issues that drugs like Effexor incur on a significant percentage of patients.

"Patel Carolina & Associates PLLC" filed a lawsuit in 2004 due to the discontinuation side effects of the drug.

Footnotes

  1. Tamam L, Ozpoyraz N. Selective serotonin reuptake inhibitor discontinuation syndrome: a review. Adv Ther 19 (1): 17-26. PMID 12008858.
  2. 2.0 2.1 2.2 Haddad P (2001). Antidepressant discontinuation syndromes. Drug Saf 24 (3): 183-97. PMID 11347722.
  3. 3.0 3.1 Fava M, Mulroy R, Alpert J, Nierenberg A, Rosenbaum J (1997). Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine. Am J Psychiatry 154 (12): 1760-2. PMID 9396960.
  4. 4.0 4.1 4.2 Parker G, Blennerhassett J (1998). Withdrawal reactions associated with venlafaxine. Aust N Z J Psychiatry 32 (2): 291-4. PMID 9588310.
  5. van Noorden M, Vergouwen A, Koerselman G (2002). [Delirium during withdrawal of venlafaxine]. Ned Tijdschr Geneeskd 146 (26): 1236-7. PMID 12132141.
  6. Nissen C, Feige B, Nofzinger E, Riemann D, Berger M, Voderholzer U (2005). Transient narcolepsy-cataplexy syndrome after discontinuation of the antidepressant venlafaxine. J Sleep Res 14 (2): 207-8. PMID 15910521.
  7. 7.0 7.1 Baboolal N (2004). Venlafaxine withdrawal syndrome: report of seven cases in Trinidad. J Clin Psychopharmacol 24 (2): 229-31. PMID 15206672.
  8. Reeves R, Mack J, Beddingfield J (2003). Shock-like sensations during venlafaxine withdrawal. Pharmacotherapy 23 (5): 678-81. PMID 12741444.

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