SEROXAT AND OTHER SSRIs

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Posts Tagged ‘Paroxetine’

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

Posted in Paroxetine, SSRIs | Tagged: , , , , , | 1 Comment »

Possible legal action – Quote from 10 years ago

Posted by shutah on January 22, 2011

More than 60 people in Britain who say they have become hooked on the anti-depressant Seroxat – a drug in the Prozac class – are exploring the possibility of legal action against the pharmaceutical company which they claim failed to warn doctors that that it could create dependency.

Two firms of solicitors say they already have between 30 and 40 cases each. The people have come forward following news of a legal case in the US in which 35 people allege they suffered severe side-effects when they tried to stop taking the drug.

The Los Angeles law firm Baum, Hedlund, Aristei, Guilford and Schiavo – which filed its action against the British manufacturers GlaxoSmithKline in September – has since had more than 2,000 calls from people to tell of their addiction to the drug, which is known in the US as Paxil. The side-effects they suffer when they try to stop taking the tablets, include jolting pains in the head, vertigo, loss of coordination, abdominal discomfort, agitation and confusion.

The US lawyers have asked GSK to set up treatment centres to help people attempting to withdraw from Paxil/Seroxat. GSK say there is no reliable scientific evidence that the drug causes addiction or dependency.

The British solicitors, Ross & Co, based in the Wirral, and Hugh James Ford Simey of Cardiff, have been receiving calls from people who did not realise that others had suffered the same symptoms when they tried to cut down and come off the drug.

“We have been contacted by 30 to 40 people, most of whom have startlingly similar tales to tell of being put on the drug and being taken off it, and then going back on,” said Mark Harvey of Hugh James Ford Simey.

Mr Harvey said most people are told by the doctor that their problems are the symptoms of their depression re-appearing and do not suspect that the drug might be to blame. “This does have the smell of something that is a problem,” he said. “The patient information sheet says it is not addictive twice.”

Graham Ross, of Ross & Co, thinks that there is a good potential case against the manufacturers. “So far as evidence of dependency is concerned, that is pretty strong,” he said.

“I feel we can prove that. Failure to ensure that GPs are aware of that risk and therefore warn patients accordingly – there is plenty of evidence that they are not doing that.”

But group actions face particular problems in Britain. Attempts to litigate against the makers of benzodiazapines – including Valium, Librium and Ativan, which were also said not to be addictive when they were launched – collapsed because the legal aid granted to the claimants was used up in the lengthy investigations of the cases demanded by the companies before the action reached court.

Posted in GlaxoSmithKline, GSK, Paroxetine, Paxil, Seroxat, Seroxat Legal, SSRIs, Withdrawal | Tagged: , , , , , , , , | 1 Comment »

Paroxetine: 1991 review….

Posted by shutah on January 18, 2011

Drugs. 1991 Feb;41(2):225-53.

Paroxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness.

Dechant KLClissold SP.

Adis Drug Information Services, Auckland, New Zealand.

Abstract

Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin, thereby facilitating serotoninergic transmission; this action appears to account for the antidepressant activity observed with this drug.  A mean terminal elimination half-life of approximately 24 hours permits once daily administration.

Results of short term clinical trials have shown paroxetine to be significantly superior to placebo, and comparable to amitriptyline, clomipramine, imipramine, dothiepin and mianserin in relieving symptoms associated with major depressive disorders.

Paroxetine has shown some preliminary promise in the treatment of depressive illness resistant to tricyclic antidepressant therapy but further studies are required before any conclusions can be drawn.

Paroxetine in therapeutic doses has been very well tolerated, and the favourable tolerability profile of this agent appears to be its primary advantage over traditional antidepressant agents.

Paroxetine causes minimal anticholinergic-type adverse effects, and unlike tricyclic antidepressants, it does not precipitate cardiovascular effects or provoke cardiac conduction disturbances. Nausea has been the most frequently reported adverse event during short term use of paroxetine, but it is generally mild and transient and subsides with continued use. With longer term use headache, sweating and constipation were the most frequently reported side effects but the incidence rate was not significantly different from that noted for comparator antidepressants.  Furthermore, the frequency of withdrawal due to adverse effects is less with paroxetine than with tricyclic antidepressant agents.

Overall, available data appear to indicate that while the efficacy of paroxetine is similar to that of traditional antidepressant drugs, the newer agent possesses much improved tolerability.

In addition, the wide therapeutic index of paroxetine may be beneficial when treating patients with an increased risk of suicide.

Thus, paroxetine clearly looks to become a valuable addition to the range of drugs currently available to treat depressive illness. Future research may help to further define the relative place of this newer agent in antidepressant therapy and determine how its overall therapeutic efficacy compares with that of other related antidepressant agents such as fluoxetine.

 

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Clinical Pharmacology of SSRI’s

Posted by shutah on January 16, 2011

Whilst a technical piece of information, this document highlights the differences between the various  SSRIs .

“The half-life of paroxetine is a function of its plasma drug level. Following a single 20 mg dose, paroxetine has a half-life of 10 hours (Table 6.4). Paroxetine does not reach a half-life of 20 hours until steady-state has been reached on 20 mg/day (Table 6.4) because paroxetine inhibits CYP 2D6, which is the CYP enzyme responsible for its biotransformation. When paroxetine levels fall after this drug is discontinued, its clearance rate increases as the inhibition of the enzyme is decreased. Thus, paroxetine and fluvoxamine are more quickly cleared from the body than the other SSRIs. “

 

 

Posted in Paxil, Seroxat, SSRIs, Withdrawal | Tagged: , , , | Leave a Comment »