Fluoxetine in panic disorder

Citalopram and fluoxetine also have been studied in panic disorder (Michelson et al. 1998 Wade et al. 1997). Citalopram was compared with clomipramine. At the most effective citalopram dose (20-30 mg/day), approximately 58% of patients were panic-free compared with 50% of patients receiving clomipramine and 32% of placebo patients. All rating scales suggested that 20 or 30 mg/day of citalopram was more effective than 40 or 60 mg/day of citalopram. Finally, data support the efficacy of fluoxetine in panic disorder. In a study comparing 10 and 20 mg/day of fluoxetine and placebo, fluoxetine treatment, particularly the 20-mg daily dose, was associated with more improvement than placebo across multiple measures, including functional impairment. 

Schneier FR, Liebowitz MR, Davies SO, et al. Fluoxetine in panic disorder. J Clin Psychopharmacol 1990 10 119-121. 

Pecknold JC, Luthe L, Iny L, Ramdoyal D. Fluoxetine in panic disorder pharmacologic and tritiated platelet... 

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... 

Coplan JD, Papp LA, Pine DS, et al Clinical improvement with fluoxetine therapy normalizes noradrenergic function in panic disorder. Paper presented at the annual meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico, December 1995a... 

Coplan JD, Papp LA, Martinez J, et al Persistence of blunted human growth hormone response to clonidine in panic disorder following fluoxetine treatment. Am J Psychiatry 152 619-622, 1995c... 

Markovitz PJ, Stagno SJ, Calabrese JR Buspirone augmentation of fluoxetine in obsessive-compulsive disorder. Am J Psychiatry 147 798-800, 1990 Markowitz JS, Weissman PH, Ouelette R, et al Quality of life in panic disorder. Arch Gen Psychiatry 46 984-992, 1989... 

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). 

Emmanuel NP, Ware MR, Brawman-Mintzer O, et al. Once-weekly dosing of fluoxetine in the maintenance of remission in panic disorder. J Clin Psychiatry 1999 60 299-301. 

Michelson D, Lydiard RB, Pollack MH, Tamura RN, Hoog SL, Tepner R, Demi track MA, Tollefson GD (1998) Outcome assessment and clinical improvement in panic disorder evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study Group. Am J Psychiatry 155 1570-1577... 

The initial dose of SSRI is similar to that used in depression. Patients should be titrated as tolerated to response. Many patients will require maximum recommended daily doses. Patients with comorbid panic disorder should be started on lower doses (Table 37-4). When discontinuing SSRIs, the dose should be tapered slowly to avoid withdrawal symptoms, with the possible exception of fluoxetine. Relapse rates may be as high as 50%, and patients should be monitored closely for several weeks.58 Side effects of SSRIs in SAD patients are similar to those seen in depression and most commonly include nausea, sexual dysfunction, somnolence, and sweating. 

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. 

Ribeiro L, Busnello J, Kauer-Sant Anna M, Madruga M, Quevedo J, Busnello E (2001) Mir-tazapine versus fluoxetine in the treatment ot panic disorder. Braz J Med Biol Res 34 1303-1307... 

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. 

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 ... 

Psychiatr Chn North Am 19 179-200, 1996 Fava M, Rosenbaum JF, McGrath PJ, et al Dthium and tricyclic augmentation of fluoxetine treatment for resistant major depression a double-blind, controlled study. Am J Psychiatry 151 1372-1374, 1994 Fawcett J Suicide risk factors in depressive disorders and panic disorder. J Clin Psychiatry 53 [suppl 3) 9-13, 1992... 

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,... 

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)... 

Therapeutic uses The primary indication for fluoxetine is depression, where it is as effective as the tricyclic antidepressants. Fluoxetine is effective in treating bulimia nervosa and obsessive-compulsive disorder. The drug has been used for a variety of other indications, including anorexia nervosa, panic disorder, pain associated with diabetic neuropathy, and for premenstrual syndrome. 

Gorman et al. (1987) conducted an open trial of fluoxetine involving 16 patients with panic disorder. They reported, Two of the nonresponders became depressed and had suicidal ideation while taking fluoxetine. Only one of the two had a history of depression (p. 331). Still in the era before recognition of SSRI-induced suicidality, the authors did not comment on this finding. 

Obsessive compulsive disorder, panic disorder, generalized anxiety disorder, bulimia nervosa, social anxiety disorders, post-traumatic stress disorder, dementia, dysthymia, premature ejaculation. Citalo-pram (investigational) is used for dementia, smoking cessation, ethanol abuse, OCD in children with diabetic neuropathy. Sertraline and Sarafem (contains fluoxetine) are also used to treat premenstrual dysphoric disorder. 

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