Panic disorder paroxetine

Panic disorder Paroxetine (immediate- and controlled-release), sertraline, fluoxetine. 

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 current SSRIs in the United States inclnde fluoxetine, fluvoxamine, sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro). All effectively treat major depression. In addition, one or more of the SSRIs has been shown effective in the treatment of dysthymic disorder, the depressive phase of bipolar disorder, premenstrual dysphoric disorder, panic disorder, social phobia, obsessive-compnlsive disorder, bnlimia nervosa, and binge-eating disorder. 

Newer Generation Antidepressants. All SSRIs have been shown effective in the treatment of panic disorder. Of these, flnoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft), as well as the SNRI venlafaxine ER (Effexor XR), have received FDA approval for the treatment of panic disorder. Because they are safer and easier to tolerate, SSRls/SNRls have largely supplanted the MAOIs and TCAs as standard treatments (along with benzodiazepines) for panic disorder. 

SSRI/SNRI GAD OCD Panic disorder PTSD Social anxiety disorder Onset worsening side-effects on initiation few long-term effects Relatively safe in overdose (venlafaxine possibly less safe) Well-described more common with paroxetine uncommon with fiuoxetine... 

Lecrubier Y, Judge R (1997) Long-term evaluation of paroxetine, clomipramine and placebo in panic disorder. Collaborative Paroxetine Panic Study Investigators. Acta Psychiatr Scand 95 153-160... 

Oehrberg S, Christiansen PE, Behnke K, Borup AL, Severin B, Soegaard J, Calberg H, Judge R, Ohrstrom JK, Manniche PM (1995) Paroxetine in the treatment of panic disorder. A randomised, double-blind, placebo-controUed study. Br J Psychiatry 167 374-379... 

StrOhle A, Pasini A, Romeo E, Hermann B, Spalletta G, di Michele F, Holsboer F, Rupprecht R (2000) Fluoxetine decreases concentrations of 3a,5a-tetrahydrodeoxycorticosterone (3a,5a-THDOC) in major depression. J Psychiatr Res 34 183-186 StrOhle A, Kellner M, Holsboer F, Wiedemann K (2001) Anxiolytic activity of atrial natriuretic peptide in patients with panic disorder. Am J Psychiatry 158 1514-1516 StrOhle A, Romeo E, di Michele F, Pasini A, Yassouridis A, Holsboer F, Rupprecht R (2002) GABAA receptor modulatory neuroactive steroid composition in panic disorder and during paroxetine treatment. Am J Psychiatry 159 145-147 StrOhle A, Romeo E, di Michele F, Pasini A, Hermann B, Gajewsky G, Holsboer F, Rupprecht F (2003) Induced panic attacks shift GABAA receptor modulatory neuroactive steroid composition. Arch Gen Psychiatry 60 161-168 Szapiro G, Vianna MRM, McGaugh JL, Medina JH, Izquierdo I (2003) The role of NMDA glutamate receptors, PKA, MAPK, and CAMKII in the hippocampus in extinction of conditioned fear. Hippocampus 13 53-58... 

Panic disorder. Sixty-six panic disorder patients were included in a study. All of whom met the DSM-IV diagnosis of panic disorder (n = 45) or panic disorder with agoraphobia ([PDA] n = 21). Twenty-four patients experienced their first panic attack within 48 hours of cannabis use and then went on to develop panic disorder. All the patients were treated with paroxetine (gradually increased up to 40 mg/day). The two groups responded equally well to paroxetine treatment as measured at the 8 weeks and 12 months follow-up visits. There were no significant effects of age, sex, and duration of illness as covariates with response rates between the two groups. In addition, panic disorder or panic disorder... 

In a randomized, double-blind, placebo-controlled study of paroxetine treatment of panic disorder in adults, 12 weeks of treatment was followed by 2 weeks of placebo (Oehrberg et ah, 1995). In this placebo period, 19 patients out of 55 (34.5%) who had received paroxetine reported an adverse event on discontinuation, compared to 7 out of 52 (13.5%) patients who had received placebo. The most common discontinuation complaint was dizziness. 

Of the SSRIs, fluoxetine has been studied most extensively. Birmaher et al. (1994) and Fairbanks et al. (1997) both found significant improvement in various anxiety disorder symptoms in typically developing children. Fluoxetine was also found to be effective in the treatment of selective mutism (Black and Udhe, 1994 Dummit et ah, 1996). Fluoxetine has also been studied in individuals with MR and autistic disorder. In an open trial. Cook et al (1992) found that fluoxetine was associated with significant improvement in the Clinical Global Impression (CGI) severity ratings in 15 of 23 individuals (65%) with autistic disorder and in 10 of 16 individuals (62%) with MR. All of the SSRIs appear to have similar properties and have been approved for panic disorder, phobias, OCD, and anxiety disorder. Sertraline has been approved for treatment of PTSD, and paroxetine, for social phobia. 

For the treatment of panic disorder, sertraline is generally started at 25 mg per day for the first week, and subsequently increased to 50 mg once a day as needed. Side effects are the same as those described above for paroxetine. 

A meta-analysis (Boyer 1995) has compared some serotonin reuptake inhibitors (paroxetine, fluvoxamine, zimeldine, and clomipramine) with imipramine and alprazolam in the alleviation of panic attacks in patients with DSM-III or DSM-III-R panic disorder. Although all three classes of drugs were shown to be significantly more effective than placebo, the serotonin reuptake inhibitors were also significantly superior to both imipramine and alprazolam. The findings of this meta-analysis highlight the importance of... 

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 ... 

Ballenger JG, McDonald S, Noyes R, et al The first double bhnd, placebo controlled trial of a partial benzodiazepine agonist abecarnil (ZK 112-119) in generalized anxiety disorder. Psychopharmacol Bull 27 171-179, 1991 Ballenger JG, Wheadon DE, Steiner M, et al Double-blind, fixed-dose, placebo-con-trolled study of paroxetin in the treatment of panic disorder. Am J Psychiatry 155 36-42, 1998... 

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. 

Lecrubier Y, Judge R Long-term evaluation of paroxetine, clomipramine and placebo in panic disorder. Acta Psychiatr Scand 95 153-160, 1997 Lecrubier Y, Puech AJ, Azcona A, et al A randomized double-blind placebo-con-trolled study of tropisetron in the treatment of outpatients with generalized anxiety disorder. Psychopharmacology 112 129, 1993 Lecrubier Y, Pletan Y, Selles A, et al Clinical efficacy of milnacipran placebo-con-trolled trials. Int Chn Psychopharmacol 11 (suppl 4 29-34, 1996 Lecrubier Y, Bakker A, Dunbar G, et al A comparison of paroxetine, clomipramine and placebo in the treatment of panic disorder. Acta Psychiatr Scand 95 145-152, 1997... 

A larger set of placebo-controlled studies show conclusively that imipramine is also effective for the treatment of panic disorders. Other agents shown to be effective in panic disorders include the SSRIs paroxetine, sertraline, fluvoxamine, fluoxetine and citalopram. Generally, initial treatment of moderate to severe panic disorders may require the initiation of a short course of benzodiazepines e.g. clonazepam (0.5 1 mg twice daily), and an SSRI. The patient will obtain immediate relief from panic attacks with the benzodiazepine whereas the SSRI may take 1 6 weeks to become effective. Once a patient is relieved of initial panic attacks, clonazepam should be tapered and discontinued over several weeks and SSRI therapy continued thereafter. There are no pharmacological treatments available for specific phobias, however controlled trials have shown efficacy for several agents, e.g. phenelzine, moclobemide. clonazepam, alprazolam, fluvoxamine. sertraline and paroxetine in the treatment of social phobia (Roy-Byrne and Cowlev, 2002). 

Bell, C, Forshall, S, Adrover, M., et aI Does 5-HT restrain panic A tryptophan depletion study in panic disorder patients recovered on paroxetine. J. Psychopharmacol. 16(1), 5-14, 2002. 

Foster RH, Goa KL. Paroxetine a review of its pharmacology and therapeutic potential in the management of panic disorder. CNS Drugs 1997 8 163-188. 

Bakker A, van Dyck R, Spinhoven P, et al. Paroxetine, clomipramine, and cognitive therapy in the treatment of panic disorder. J Clin Psychiatry 1999 60 831-838. 

The selective serotonin reuptake inhibitors (SSRIs) represent a chemically diverse class of agents that have as their primary action the inhibition of the serotonin transporter (SERT) (Figure 30-3). Fluoxetine was introduced in the United States in 1988 and quickly became one of the most commonly prescribed medications in medical practice. The development of fluoxetine emerged out of the search for chemicals that had high affinity for monoamine receptors but lacked the affinity for histamine, acetylcholine, and adrenoceptors that is seen with the tricyclic antidepressants (TCAs). There are currently six available SSRIs, and they are the most common antidepressants in clinical use. In addition to their use in major depression, SSRIs have indications in GAD, PTSD, OCD, panic disorder, PMDD, and bulimia. Fluoxetine, sertraline, and citalopram exist as isomers and are formulated in the racemic forms, whereas paroxetine and fluvoxamine are not optically active. Escitalopram is the S enantiomer of citalopram. As with all antidepressants,... 

Some anxiety disorders may require higher doses of antidepressants than are used in the treatment of major depression. For example, patients treated for OCD often require maximum or somewhat higher than maximum recommended MDD doses to achieve optimal benefits. Likewise, the minimum dose of paroxetine for the effective treatment of panic disorder is higher than the minimum dose required for the effective treatment of 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)... 

Kim EJ, Yu B-H. Increased cholesterol levels after paroxetine treatment in patients with panic disorder. I Clin Psychopharmacol 2005 25 597-9. 

Antidepressant drugs, however, might have direct anxiolytic effects. That is, certain antidepressants such as paroxetine (Paxil) or venlafaxine (Effexor) can help reduce anxiety independent of their effects on depression.1,47 These antidepressants have therefore been advocated as an alternative treatment for anxiety, especially for people who cannot tolerate the side effects of traditional anxiolytics, or who might be especially susceptible to the addictive properties of drugs like the benzodiazepines.1,9,46 Moreover, antidepressants such as paroxetine or venlafaxine are now considered effective as the primary treatment for several forms of anxiety, including generalized anxiety disorder, social phobia, and panic disorder.4,29,53 Antidepressants, either used alone or in combination with antianxiety drugs, have become an important component in the treatment of anxiety. 

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