Obsessive-compulsive disorder paroxetine

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

The enantiomerically pure 3-arylglutaric ester are precursors for the synthesis of (—)-paroxetine [10], a selective serotonin reuptake inhibitor used in the treatment of depression, obsessive compulsive disorder, and panic, and (i )-Baclofen [11], a GABAb receptor agonist, which is used cHnically in the treatment of spasticity (Chart 5.1). 

Seroxat (Paroxetine) Depression Obsessive-compulsive disorders Panic Post-traumatic stress disorder 2.1 0.7 1991 - UK 1993 - US Once daily... 

Like sertraline, these two drugs are selective serotonin reuptake inhibitors. Fluoxetine is prescribed for depression, bulimic binge-eating and vomiting, obsessive-compulsive disorder, obesity, alcoholism, and anorexia among other ailments. Paroxetine is used for depression and obsessive-compulsive disorder. Interestingly the three top antidepressants are chemically unrelated to each other, except for being amines, and are unrelated to earlier tricyclic antidepressants. 

Citalopram, escitalopram, and paroxetine are not approved for use in pediatric patients. Fluoxetine is approved for use in pediatric patients with MDD and obsessive-compulsive disorder (OCD). Sertraline is not approved for use in pediatric patients except for patients with OCD. Fluvoxamine is not approved for use in pediatric patients except for patients with OCD. 

Obsessive-compulsive disorder (OCD) Fluoxetine fluvoxamine paroxetine (immediate-release), sertraline. 

Due to the frequent unwanted effects and, in case of tranylcypromine, the numerous and dangerous interactions MAO-inhibitors are more and more replaced by the much less problematic SSRIs. Compounds belonging to this group are citalopram, escitalopram, fluoxetine, paroxetine and sertraline. They are used clinically in the therapy of depression, bulimia and obsessive-compulsive disorders. All SSRIs show a slow onset of action (1-2 weeks). They may induce insomnia and weight loss. The antidepressant ven-lafaxine inhibits both, serotonin and noradrenaline re-uptake and might therefore additionally induce hypertension. 

In 1987, the FDA approved the drug fluoxetine (Prozac) for use in the treatment of major depression. Fluoxetine belongs to a class of agents referred to as selective serotonin reuptake inhibitors (SSRIs). The SSRIs now include sertraline (Zoloft), fiuvoxamine (Luvox), paroxetine (Paxil), and citalopram (Celexa). Fiuvoxamine is approved for use only in obsessive-compulsive disorder and is not discussed in this chapter. 

Rosenberg, D.R., MacMaster, F.P., Keshavan, M.S., Fitzgerald, K.D., Stewart, C.M., and Moore, G.J. (2000) Decrease in caudate glu-tamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. / Am Acad Child Adolesc Psychiatry 39 1096—1103. 

FIGURE 39.2 Treatment algorithm for pediatric obsessive-compulsive disorder (OCD). In adjusting cognitive behavior therapy (CBT), increase frequency or intensity, or alter the setting or format, e.g., have it be home based or day treatment. CMI, clomipramine DMI, desipramine NT, nortriptyline SSRI, selective serotonin reuptake inhibitor (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram). 

Note. BROF = brofaromine CIT = citalopram CLO = clomipramine CT = cognitive therapy Dx = diagnosis EXP = exposure in vivo FLU = fluvoxamine FLUOX = fluoxetine GAD = generalized anxiety disorder 5-HTP = 5-hydrox3rtryptophan IMl = imipramine MAP = maprotiline OCD = obsessive-compulsive disorder PAR = paroxetine PD = panic disorder PLA = placebo PPM = psychological panic management RIT = ritanserin ... 

Paroxetine. Paroxetine, also a serotonin reuptake inhibitor, has been the subject of a case report in two subjects. Ringold [1994] reported the effective treatment of two individuals who had not responded to prior therapy with fluoxetine and sertraline. Both individuals had comorbid psychiatric problems. Subject A demonstrated both social phobia and dysthymia. Although her symptoms of dysthymia were clinically responsive to fluoxetine therapy, her social phobia symptoms were resistant. Subject B had body dysmorphic disorder, obsessive-compulsive disorder, and social phobia. His obsessive-compulsive disorder symptoms benefited from fluoxetine therapy, but his social anxiety was resistant. Sertraline therapy was attempted in both subjects. Subject A required discontinuation because of adverse effects. Subject B experienced a worsening of both obsessive-compulsive disorder and social phobia symptoms. Both subjects demonstrated a positive response in their symptoms when switched to paroxetine [20 mg/day]. 

Jenike MA, Rauch SL, Cummings JL, et al Recent developments in neurobiology of obsessive-compulsive disorder. J Clin Psychiatry 57 492-503, 1996 Jenner PN Paroxetine an overview of dosage, tolerability, and safety. Int Clin Psychopharmacol 6 [suppl 4) 69-80, 1992... 

Joyce D, Hurwitz HMB Avoidance behaviour in the rat after 5-hydroxytryptophan (5-HTP) administration. Psychopharmacologia 5 424-430, 1964 Joyce EM The neurochemistry of Korsakoff s syndrome, in Cognitive Neurochemistry. Edited by Stahl SM, Iversen SD, Goodman EC. Oxford, England, Oxford Science Publications, 1987, pp 327-345 Judd EK, Chua P, Lynch C, et al Eenfluramine augmentation of clomipramine treatment of obsessive compulsive disorder. Aust N Z J Psychiatry 25 412-414, 1991 Judge R, Steiner M The long-term efficacy and safety of paroxetine in panic disorder. 

Wheadon DE, Bushnell WD, Steiner M A fixed dose comparison of 20, 40, or 60 mg paroxetine to placebo in the treatment of obsessive-compulsive disorder [abstract). Paper presented at the annual meeting of the American College of Neuropsychopharmacology, Honolulu, HI, December 1993 Wheatley D Trazodone in depression. International Pharmacopsychiatry 15 240-246, 1980... 

Zimelidine was the first serotonin reuptake inhibitor available for clinical use, but in 1982 was withdrawn worldwide because of its toxicity ( 110). Despite this initial setback, five members of this class have been marketed in the United States and various countries around the world citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). All except fluvoxamine have marketed indications in the United States for the treatment of major depression. Fluvoxamine is marketed in the United States for the treatment of obsessive-compulsive disorder rather than major depression, although it is marketed in a number of other countries for major depression. 

Fluoxetine Highly selective blockade of serotonin transporter (SERT) little effect on norepinephrine transporter (NET) Acute increase of serotonergic synaptic activity slower changes in several signaling pathways and neurotrophic activity Major depression, anxiety disorders panic disorder obsessive-compulsive disorder post-traumatic stress disorder perimenopausal vasomotor symptoms eating disorder (bulimia) Half-lives from 15-75 h oral activity Toxicity Well tolerated but cause sexual dysfunction Interactions Some CYP inhibition (fluoxetine 2D6, 3A4 fluvoxamine 1A2 paroxetine 2D6)... 

In these trials, hostile events are found to excess in both adults and children on paroxetine compared with placebo, and are found across indications, and both on therapy and during withdrawal. The rates were highest in children with obsessive compulsive disorder (OCD), where the odds ratio of a hostile event was 17 times greater (95% confidence interval [Cl], 2.22-130.0). 

Gilbert, A., Moore, G., Keshavan, M., Paulson, L., Narula, V., Mac Master, P., et al. (2000). Decreased thalamic volumes of pediatric patients with obsessive-compulsive disorder who are taking paroxetine. Archives of General Psychiatry, 57, 449—456. 

Goder, R., Friege, L., Treskov, V., Grohmann, R., Aldenhoff, J. (2000). Association of paroxetine with suicide attempt in obsessive-compulsive disorder. Pharmacopsychiatry, 33, 116-117. 

In three children (two aged 9 years and one aged 10 years) who took paroxetine 10-20 mg/day for the treatment of childhood obsessive-compulsive disorder, symptoms of mania, including overactivity, pressure of speech, irritability, and antisocial behavior, occurred within 3 weeks of starting paroxetine and remitted after paroxetine withdrawal or dosage reduction (7). Symptoms of mania are rare in childhood, suggesting that the elevated mood in these cases was a direct effect of the paroxetine. 

A 20-year-old woman taking paroxetine 10 mg/day for obsessive-compulsive disorder developed multiple purple lesions on the fingers of both hands after 15 weeks (15). The lesions disappeared after 1 week but returned in 2 days after rechallenge with paroxetine. 

There have been reports that selective serotonin reuptake inhibitors, which inhibit CYP1A2, increase plasma olanzapine concentrations (SEDA-24, 71 SEDA-26, 63). In a recent open add-on trial, 21 patients with obsessive-compulsive disorder unresponsive to treatment with paroxetine 60 mg/day for at least 12 weeks, took additional olanzapine 10 mg/day (280). Steady-state plasma concentrations of paroxetine were not changed, and 7 patients were rated as responders at final evaluation. Sedation (n = 12), weight gain up to 3 kg (n = 8), dry mouth (n = 6), and constipation (n = 3) were the most frequent adverse effects. 

D Amico G, Cedro C, Muscatello MR, Pandolfo G, Di Rosa AE, Zoccali R, La Torre D, D Arrigo C, Spina E. Olanzapine augmentation of paroxetine-refractory obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2003 27 619-23. 

Fluoxetine (9) Fluvoxamine (10) Paroxetine (18) Sertraline (22) Bulimia nervosa, obsessive compulsive disorder (OCD), panic disorder OCD OCD,panic disorder, social anxiety disorder OCD,panic disorder, posttraumatic stress syndrome... 

Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed medications. Their therapeutic actions are diverse, ranging from efficacy in depression to obsessive-compulsive disorder, panic disorder, bulimia, and other conditions. They include bupropion, fluoxetine, nefazodone, paroxetine, and miscellaneous other drugs. 

Mundo E, Bianchi L, Bellodi L. Efficacy of fluvoxamine, paroxetine, and citalopram in the treatment of obsessive-compulsive disorder. J Qin Psychopharmacol 1997 17 267-271. 

Deny s D, vanMegen H JGM, van der Wee N, Westenberg HGM. A doubleblind switch study of paroxetine and venlafaxine in obsessive-compulsive disorder. J Clin Psychiatry 2004 65 37-43. 

PMDD is not the only mental disorder that can be treated with SSRIs. There are many kinds of syndromes that SSRIs have been approved to treat. These syndromes include eating disorders, obsessive-compulsive disorder, post-traumatic stress disorder, panic disorder, and generalized anxiety disorder. Although each SSRI would probably be just as effective in treating these syndromes, the companies that own them have done extensive research to find a niche for their drug. Thus some SSRIs, such as Paxil (paroxetine), are approved for social phobia simply because the company that owns them has done the clinical studies proving it is effective and therefore should be licensed for it. Indeed, there seems to be no end to syndrome niche markets in which SSRIs can be effective. There are now efforts to market some SSRIs as treatments... 

Paxil paroxetine SSRI depression, obsessive-compulsive disorder nausea, diarrhea, weight loss, insomnia, upset stomach, excess sweating, jitteriness... 

Paroxetine (brand name Paxii) One of the new classes of atypical antidepressant drugs that function as a serotonin reuptake inhibitor in producing a therapeutic effect. Also used to treat panic disorder and obsessive-compulsive disorder. 

Selective serotonin reuptake inhibitors (SSRIs) A relatively new group of medicines that have been used successfully to treat emotional and behavioral problems such as depression, panic disorder, obsessive-compulsive disorder ((XID), bulimia, and posttraumatic stress disorder in adults. These medications are now being used to treat the same types of behavior in children. Some examples of SSRIs include Prozac (fluoxetine), Zoloft (sertraline), Luvox (fluvoxamine), and Paxil (paroxetine). 

Paroxetine is a selective serotonin reuptake inhibitor that blocks reuptake of serotonin, enhancing serotonergic function. It is used to treat panic disorder or social anxiety disorder (except Pexeva), as defined in the DSM-IV major depressive disorder, as defined in DSM-111 (immediate release) orDSM-lV (controlled release). Immediate release only for obsessive-compulsive disorder (OCD) generalized anxiety disorder (GAD) (except Pexeva) posttraumatic stress disorder (PTSD), as defined in the DSM-IV (except Pexeva). 

---