SEROXAT AND OTHER SSRIs

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Posts Tagged ‘Citalopram’

SSRI Comparison Facts

Posted by shutah on February 14, 2011

Comparison of Selective Serotonin Reuptake Inhibitors (SSRIs)

Efficacy and effectiveness

Clinical trials comparing one SSRI with another indicate that drugs in this class are equally efficacious. Each antidepressant produces approximately a 60% overall response rate (ie, at least a 50% reduction in symptoms as a result of treatment). However, some differences in the SSRIs efficacy exist.

Escitalopram may be superior in efficacy compared with other SSRIs in the treatment of major depressive disorder2. Also escitalopram has better efficacy in the treatment of severe depression than citalopram4.  A major consideration with escitalopram is that it is not yet available in lower-cost generic form. The drug is still under patent. In 2006 Forest Laboratories was granted an 828 day (2 years and 3 months) extension on its patent for escitalopram31. This pushed the patent expiry from December 7, 2009 to March 14, 2012.

Paroxetine, fluoxetine, and sertraline are similar in effectiveness for major depression and depression with high levels of anxiety3,5.

Paroxetine is the only SSRI indicated for all five anxiety disorders in addition to major depressive disorder.

Fluoxetine has a slower onset of antidepressants effect than other SSRIs4. Also, fluoxetine appears to be somewhat less effective, than other drugs in this class24,25.

Sertraline may have a slightly higher rate of response than fluoxetine and paroxetine26. Sertraline has advantages over paroxetine in the treatment of panic disorder27.

Interesting and important fact is that SSRI antidepressants are not interchangeable. Persons who discontinue one SSRI for lack of tolerability or response can be effectively treated with another19.

Discontinuation symptoms (withdrawal)

SSRIs aren’t considered addictive.  YET !! However, stopping treatment abruptly or missing several doses can cause withdrawal-like symptoms, including nausea, headache, dizziness, lethargy and flu-like symptoms. This is sometimes called discontinuation syndrome.

All antidepressants do not have the same type or severity of withdrawal symptoms. Discontinuation syndrome is more common with the SSRIs with shorter half lives and inactive metabolites, such as paroxetine, sertraline, and fluvoxamine. The incidence of discontinuation syndrome is highest with paroxetine followed by fluvoxamine and sertraline. Citalopram and fluoxetine have a lower occurrence of withdrawal symptoms10.

Abrupt interruption of antidepressant therapy for 5-8 days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline, with few symptoms seen with fluoxetine12.

Pregnancy category

All SSRIs (except paroxetine) are classified as pregnancy Category C, meaning that they may not be safe for use during pregnancy.

Paroxetine (Paxil, Paxil CR) is pregnancy Category D medication. Paroxetine may cause heart defects or serious, life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy.

Pharmacology

Selective serotonin reuptake inhibitors differ in their potency and selectivity in inhibiting serotonin reuptake and there may be important effects on other transporters and receptors, indicating that they are not as selective as their manufacturers suggest. It has been proposed, for example, that fluoxetine’s effects on 5-HT2C receptors may underlie a propensity to cause agitation; paroxetine’s affinity for muscarinic receptors causes its increased tendency to produce discontinuation effects; sertraline’s affinity for the dopamine transporter results in a greater efficacy in severe depression; and sertraline’s and fluvoxamine’s affinity for sigma1 opioid receptors is responsible for their efficacy in psychotic depression (Goodnick & Goldstein, 1998a).

Half-life

The half-life of a drug is the time required to achieve steady-state plasma concentrations (i.e., to metabolize half the dose and lower blood concentrations by 50%). Half-life can be used to estimate how long it will take to clear a drug from the body after treatment is discontinued.

Fluoxetine is unique because of its long half-life and the long half-life of its active metabolite norfluoxetine. Fluoxetine has a half-life of 2-4 days and its active metabolite, norfluoxetine, has a half-life of 4-16 days.

In comparison, citalopram, escitalopram, paroxetine, and sertraline have shorter half-lives in the range of 20-35 hours, and steady-state concentrations (and therapeutic effect) are reached much more rapidly. The long half-life of fluoxetine may blunt the effects of missed doses or treatment discontinuation and makes it easier to discontinue than any of the other SSRIs. On the other hand, fluoxetine requires a much longer washout period than the other SSRIs (several weeks), particularly when switching to monoamine oxidase inhibitors (MAOIs) or TCA.

Antidepressants with relatively short half-lives are desirable for people with multiple comorbidities and complex, multiple-drug regimens because they allow for once-daily dosing. A short half-life enables physicians to switch more rapidly and safely to an alternative antidepressant if treatment fails or if unfavorable drug reactions occur.

Paroxetine and fluvoxamine are more quickly cleared from the body than the other SSRIs.

The possible slower onset of antidepressant action of fluoxetine may be owing to a longer time taken to achieve therapeutic plasma concentrations. In situations where the speed of onset of therapeutic effect is particularly important, such as in severe depression, fluoxetine may not be the SSRI of choice. Patients in whom the long half-life may have advantages (and therefore for whom fluoxetine should be considered) include those who are poorly compliant and those in whom administration less frequent than daily is contemplated.

Sertraline exhibits a sex- and age-dependent half-life. In men, the half-life is approximately 30% shorter (22.4 hr) than in females or the elderly (32.1-36.7 hr).

References
  • Celexa Prescribing Information Celexa.com, Forest Pharmaceuticals, Inc.
  • Lexapro Prescribing Information Lexapro.com, Forest Pharmaceuticals, Inc.
  • Paxil Prescribing Information – Paxil.com, GlaxoSmithKline
  • Prozac Prescribing Information Prozac.com, Eli Lilly and Company
  • Zoloft Prescribing Information – Zoloft.com, Pfizer Inc.
  • 1. Side-effect profile of fluoxetine in comparison with other SSRIs, tricyclic and newer antidepressants: a meta-analysis of clinical trial data. Pharmacopsychiatry. 2005 Mar;38(2):69-77 MedLine
  • 2. Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis. J Psychiatry Neurosci. 2006 Mar;31(2):122-31. MedLine
  • 3. Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. JAMA. 2001 Dec 19;286(23):2947-55
  • 4. Escitalopram is more effective than citalopram for the treatment of severe major depressive disorder Encephale. 2004 Mar-Apr;30(2):158-66. MedLine
  • 5. Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression. J Affect Disord. 2000 Aug;59(2):119-26.
  • 6. Labbate LA. Sex and serotonin reuptake inhibitor antidepressants. Psychiatr Ann. 1999;29:571–9.
  • 7. Meijer WE, Heerdink ER, van Eijk JT, Leufkens HG. Adverse events in users of sertraline: results from an observational study in psychiatric practice in The Netherlands. Pharmacoepidemiol Drug Saf. 2002;11:655–62. PubMed
  • 8. Fava M. Weight gain and antidepressants. J Clin Psychiatry. 2000;61(Suppl.):37–41. PubMed
  • 9. Fergunson JM. SSRI antidepressant medications: adverse effects and tolerability. Primary Care Companion. J Clin Pschiatry. 2001;3:22–7.
  • 10. Schatzberg AF, Haddad P, Kaplan EM, Lejoyeux M, Rosenbaum JF, Young AH, Zajecka J. Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. Discontinuation Consensus panel. J Clin Psychiatry. 1997;58
  • 11. Westenberg HG, Sandner C. Tolerability and safety of fluvoxamine and other antidepressants. Int J Clin Pract. 2006 Apr;60(4):482-91. PubMed
  • 12. Rosenbaum JF, Fava M, Hoog SL, Ascroft RC, Krebs WB. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry. 1998 Jul 15;44(2):77-87. PubMed
  • 14. Ian M. Anderson and J. Guy Edwards. Guidelines for choice of selective serotonin reuptake inhibitor in depressive illness Advances in Psychiatric Treatment (2001) 7: 170-180
  • 15. Fava M, Judge R, Hoog SL, Nilsson ME, Koke SC. Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. J Clin Psychiatry. 2000 Nov;61(11):863-7.PubMed
  • 16. Montejo-Gonzalez AL, Llorca G, Izquierdo JA, Ledesma A, Bousono M, Calcedo A, Carrasco JL, Ciudad J, Daniel E, De la Gandara J, Derecho J, Franco M, Gomez MJ, Macias JA, Martin T, Perez V, Sanchez JM, Sanchez S, Vicens E. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther. 1997 Fall;23(3):176-94.PubMed
  • 17. Maina G, Albert U, Salvi V, Bogetto F. Weight gain during long-term treatment of obsessive-compulsive disorder: a prospective comparison between serotonin reuptake inhibitors. J Clin Psychiatry. 2004 Oct;65(10):1365-71.PubMed
  • 18. Bymaster FP, Zhang W, Carter PA, Shaw J, Chernet E, Phebus L, Wong DT, Perry KW. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology (Berl). 2002 Apr;160(4):353-61.
  • 19. Nurnberg HG, Thompson PM, Hensley PL. Antidepressant medication change in a clinical treatment setting: a comparison of the effectiveness of selective serotonin reuptake inhibitors. J Clin Psychiatry. 1999 Sep;60(9):574-9.
  • 20. Stahl SM. Not so selective serotonin reuptake inhibitors. J Clin Psychiatry 1998;59:343-4. Psychiatrist
  • 21. Owens JM, Knight DL, Nemeroff CB. Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Encephale. 2002 Jul-Aug;28(4):350-5. PubMed
  • 22. Bolden-Watson C, Richelson E. Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sci. 1993;52(12):1023-9. PubMed
  • 23. Edwards JG, Anderson I. Systematic review and guide to selection of selective serotonin reuptake inhibitors. Drugs. 1999 Apr;57(4):507-33. PubMed
  • 24. Geretsegger C, Bo”hmer F, Ludwig M. Paroxetine in the elderly depressed patient: randomized comparison with fluoxetine of efficacy, cognitive and behavioural effects. Int Clin Psychopharmacol. 1994 Spring;9(1):25-9. PubMed
  • 25. Flament MF, Lane RM, Zhu R, Ying Z. Predictors of an acute antidepressant response to fluoxetine and sertraline. PubMed
  • 26. Clinical Pharmacology of SSRI’s. How SSRIs as a Group Are Similar.Sheldon H. Preskorn, M.D.
  • 27. Bandelow B, Behnke K, Lenoir S, Hendriks GJ, Alkin T, Goebel C, Clary CM. Sertraline versus paroxetine in the treatment of panic disorder: an acute, double-blind noninferiority comparison. J Clin Psychiatry. 2004 Mar;65(3):405-13 PubMed
  • 28. Montejo AL, Llorca G, Izquierdo JA, Rico-Villademoros F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psychiatry. 2001;62 Suppl 3:10-21. PubMed
  • 29. Winokur A, Lexon N, Allen K, and et al. Sertraline administered for 8 weeks to depressed patients did not alter sleep architecture: a preliminary report. New Research Program and Abstracts of the 147th Annual Meeting of the American Psychiatric Association; May 24, 1994
  • 30. Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JP, Churchill R, Watanabe N, Nakagawa A, Omori IM, McGuire H, Tansella M, Barbui C. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet. 2009 Feb 28;373(9665):746-58.
  • 31. “Forest Laboratories Receives Patent Term Extension for Lexapro” Press release

Published: May 05, 2007
Last updated: August, 2009

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‘I will write to the Medicines and Healthcare Products Regulatory Agency asking if more research is needed into the drug.’

Posted by shutah on January 13, 2011

Citalopram Inquiry:  On 7 December 2010 Birmingham Coroner Aiden Cotter said he would write to the MHRA and ask if more research is needed into this drug.  The statement was made following an inquest into the death of a 42 year old mother of two, who had committed suicide in October 2010.

Professor David Healy, an expert on anti-depressants  at Cardiff University, told the inquest he believed the drug [Citalopram]was  “likely to have played a part”.  He further added, “This is the second inquest regarding this drug I have attended in the past five months. There have also been homicide cases involving it [Citalopram].’

I will keep any eye out for the MHRA response to Coroner Cotter, but won’t hold my breath!!

Read more: http://www.dailymail.co.uk/news/article-1336514/Citalopram-inquiry-doctor-blames-anti-depressant-mothers-suicide.html#ixzz1AwSZLdtF

 

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