Panic disorder fluvoxamine

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. 

Palatnik, A., Frolov, K., Fux, M., Benjamin, J. Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder./. Clin. Psychopharmacol. 21 335-339, 2001. 

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. 

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 ... 

Bakish D, Hooper CL, Filteau MJ, et al A double-blind placebo-controlled trial comparing fluvoxamine and imipramine in the treatment of panic disorder with or without agoraphobia. Psychopharmacol Bull 32 135-141, 1996 Bakish D, Hooper CL, Thorton MD, et al Fast onset an open study of the treatment of major depressive disorder with nefazodone and pindolol combination therapy. Int Clin Psychopharmacol 12 91-97, 1997 Baldwin DS Depression and sexual function. J Psychopharmacol 10 (suppl l) 30-34, 1996... 

Black DW, Wesner R, Bowers W, et al A comparison of fluvoxamine, cognitive therapy and placebo in the treatment of panic disorder. Arch Gen Psychiatry 50 44-50, 1993... 

Hoehn-Saric R, Fawcett J, Munjack DJ, et al A multicentre, double-bhnd, placebo-controlled study of fluvoxamine in the treatment of panic disorder. Neuropsychopharmacology 10 102S, 1994... 

Holland RL Fluvoxamine in panic disorder after discontinuation Neuropsychopharmacology 10 102S, 1994... 

Van Vhet 1, Den Boer JA, Westenberg HGM A double-blind comparative study of brofaromine and fluvoxamine in outpatients with panic disorder. J Clin Psychopharmacol 16 299-306, 1996a... 

Woods SW, Black D, Brown S, et al Fluvoxamine in the treatment of panic disorder in outpatients a double-blind, placebo-controlled study. Neuropsychopharmacology 10 1038, 1994... 

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). 

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)... 

SSRIs and the benzodiazepine alprazolam are often used to treat panic disorder. Pharmacokinetic reactions between them could therefore be important. Alprazolam is metabolized by CYP3A4, which fluvoxamine inhibits (SEDA-22, 13). In 23 out-patients (11 men, 12 women, mean age 39 years) who took alprazolam both as monotherapy (mean dose 1.0 mg/day) and in combination with fluvoxamine (mean dose 34 mg/day), fluvoxamine increased plasma alprazolam concentrations by 58% (97). This was not associated with increased sleepiness, measured by a subjective rating scale, but objective measures of psychomotor function were not carried out and these could have been impaired by raised alprazolam concentrations. 

Goddard AW, Woods SW, Sholomskas DE, Goodman WK, Charney DS, Heninger GR. Effects of the serotonin reuptake inhibitor fluvoxamine on yohimbine-induced anxiety in panic disorder. Psychiatry Res 1993 48(2) 119-33. 

Yohimbine commonly causes anxiety in eight patients with panic disorder this effect was reduced by fluvoxamine (10). 

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... 

Dosing and Administration. SSRIs should be initiated at doses similar to those used for the treatment of depression and administered as a single daily dose with or without food (except for fluvoxamine). If the patient suffers from comorbid panic disorder, the SSRI dose should be started at one-fourth or one-half of the normal antidepressant dose. Patients should receive the starting dose for 2 to 4 weeks before it is increased slowly (i.e., paroxetine 10 mg/day and sertraline 50 mg/day) in weekly intervals as necessary to obtain a response. Safety for paroxetine in SAD was demonstrated in doses up to 60 mg/day, but additional therapeutic benefits above 20 mg/day were not shown. The maximum dosage of sertraline used in patients with SAD was 200 mg/day. ... 

Sandman J, Lorch B, Bandelow B, et al. Fluvoxamine or placebo in the treatment of panic disorder and relationship to blood concentration of fluvoxamine. Pharmacopsychiatry 1998 31 117-121. 

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). 

The primary uses for the SSRIs include MMD and bipolar depression (fluoxetine, paroxetine, sertraline, and citalopram), atypical depression (i.e., depressed patients with unusual symptoms, e.g., hypersomnia, weight gain, and interpersonal rejection sensitivity fluoxetine, paroxetine, sertraline, and citalopram), anxiety disorders, panic disorder (sertraline and paroxetine), dysthymia, premenstrual syndrome, postpartum depression, dysphoria, bulimia nervosa (fluoxetine), obesity, borderline personality disorder, obsessive-compulsive disorder (fluvoxamine, fluoxetine, paroxetine, and sertraline), alcoholism, rheumatic pain, and migraine headache. Among the SSRIs, there are more similarities than differences however, the differences between the SSRIs could be clinically significant. 

Several selective serotonin reuptake inhibitors (SSRIs), including escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline (Fig. 22.21), are effective as first-line treatment cf seme anxiety disorders, with the purported advantage that they lack the addictive preperties cf benzediazepines (135). Specifically, the SSRIs have been shown to be effective in obsessive-ccmpulsive diserder (139), panic disorder (140), and social phobia (141). The mechanism of action of these agents in anxiety may differ with their role in the treatment of depression however,... 

Indeed, 5-HT is also a substrate for the 5-HT transporter, itself an important player in the treatment of depression, and more recently for the whole range of anxiety disorders spectrum (GAD, OCD, social and other phobias, panic and post-traumatic stress disorders). It is the target for SSRIs (selective serotonin reuptake inhibitors) such as fluoxetine, paroxetine, fluvoxamine, and citalopram or the more recent dual reuptake inhibitors (for 5-HT and noradrenaline, also known as SNRIs) such as venlafaxine. Currently, there are efforts to develop triple uptake inhibitors (5-HT, NE, and DA). Further combinations are possible, e.g. SB-649915, a combined 5-HTia, 5-HT1b, 5-HT1d inhibitor/selective serotonin reuptake inhibitor (SSRI), is investigated for the treatment of major depressive disorder. 

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