Fluoxetine anxiety disorders

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. 

Other Antidepressants. Antidepressant refinements for the next 30 years primarily consisted of the development of new TCAs. However, in 1988, a novel antidepressant class, the selective serotonin reuptake inhibitors (SSRIs), was introduced in the United States. The chief innovation of the SSRIs was that they afforded the comparable effectiveness of the TCAs with fewer side effects and minimal toxicity. The debut of the SSRIs coincided with the reworking of the nosology of the anxiety disorders in DSM-III and DSM-IV. As a result, the SSRIs have been studied extensively in each of the respective anxiety disorders and in many cases have obtained FDA approval for the treatment of one or more of these anxiety syndromes. The SSRIs currently available in the United States include citalopram (Celexa), escitalo-pram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). 

Altemus M, Cizza G, Gold P (1992) Chronic fluoxetine treatment reduces hypothalamic vasopressin secretion in vitro. Brain Res 593 311-313 Appenrodt E, Schnabel R, Schwarzberg H (1998) Vasopressin administration modulates anxiety-related behavior in rats. Physiol Behav 64 543-547 Arborelius L, Owens MJ, PlotskyPM, Nemeroff CB (1999) The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol 160 1-12 Argiolas A, Gessa GL (1991) Central functions of oxytocin. Neurosci Biobehav Rev 15 217-231... 

Birmaher B., Waterman GS, Ryan N, Cully M, Balach L, Ingram J, Brodsky M. Fluoxetine for childhood anxiety disorders. / Am Acad Child Adolesc Psychiatry 33 993-999. 

The safety and efficacy of combined SSRI and stimulant pharmacotherapy have been addressed in two open studies. Gammon and Brown (1993) reported on the successful addition of fluoxetine to stimulants in the treatment of 32 patients with ADHD with comorbid depressive and anxiety disorders (Gammon and Brown 1993). These children with comorbid conditions had failed to respond to methylphenidate alone. Another report detailed the addition of methylphenidate to SSRI treatment (Findling, 1996). Depressed children and adults with comorbid ADHD were treated with either fluoxetine or sertraline. While depressive symptoms remitted, ADHD symptoms persisted. Methylphenidate was added and successfully treated the ADHD symptoms. In both investigations, the combined treatment was well tolerated. 

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. 

Fairbanks, J., Pine, D.S., Tancer, N.K., Dummit, E.S., Kentgen, L.M., Martin, J., Asche, B.K., and Klein, R.G. (1997) Open fluoxetine treatment of mixed anxiety disorders in children and adolescents. J Child Adolesc Psychopharmacol 17 17—29. 

In four instances, the agency has invoked this rule at the time of approval of supplements for new indications for psychotropic drugs already approved for other psychiatric indications. It was noted in the approval letters for these supplements that, since the drugs in question would likely be used in children and/ or adolescents with the newly approved indications, the FDA required the sponsors of these products to conduct studies that would be pertinent to such use in the pediatric population. Since the products were ready for approval in adults, the FDA deferred the required pediatric studies to a future date. Alternatively, sponsors could make an argument for waiver of the requirement. The drug products and indications for which the FDA has required studies under the Pediatric Rule are as follows paroxetine for social anxiety disorder sertraline for post-traumatic stress disorder (PTSD) olanzapine for acute mania in bipolar disorder and fluoxetine in premenstrual dysphoric disorder (PMDD). 

In the case of social anxiety disorder, research suggests that some of the antidepressants that are effective in other anxiety disorders do not work to ease the symptoms of social anxiety disorder. This is true of the tricyclic antidepressant imipramine and fluoxetine (Prozac). The first line of treatment for the generalized form of social anxiety disorder is an SSRI such as paroxetine or sertraline. 

Fluoxetine is manufactured by Eli Lilly under the name Prozac, as a 10-mg green football-shaped tablet or a 20-mg green and white capsule. It was the first SSRI introduced for the treatment of depression and anxiety disorders. Fluoxetine is prescribed for obsessive-compulsive disorder, the eating disorder bulimia nervosa, and panic disorder. 

Over the next 20 years, the benzodiazepines, TCAs, MAOIs, and beta-blockers were used to treat anxiety disorders. By the mid-1980s, up to 10% of all Americans were taking a benzodiazepine. In 1988, fluoxetine (Prozac) was introduced by Eli Lilly as the first selective serotonin reuptake inhibitor (SSRI) for the treatment of mood and anxiety disorders. Its success led to the development of several other SSRI drugs. Today, these drugs are the first line of drug treatment for most anxiety disorders. 

As other indications are sought for the SSRls, it is clear that their action extends beyond depression, dysthymia, and the anxiety disorders, and the broad spectrum of therapeutic action of these antidepressants becomes apparent. For example, based on the evidence from placebo-controlled studies [A. Wood 1993], fluoxetine has been licensed in Europe for the treatment of bulimia, and several SSRls are reported to be effective in the treatment of premenstrual syndrome. 

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 ... 

The selective serotonin reuptake inhibitors (SSRls) have received increased attention in the treatment of anxiety disorders. With the recent Food and Drug Administration (FDA) approval of fluoxetine and fluvoxamine in the treatment of obsessive-compulsive disorder, it has been made clear that this... 

Few trials have tested the potential efficacy of SSRIs to treat anxiety disorders other than OCD in children and adolescents. Black and colleagues ( 162) found a significant difference between fluoxetine and placebo in four of six children with selective mutism (believed to be a variant of social phobia) but only on the global rating of change and parent s rating of mutism change. In another small open-trial study, fluoxetine (10 to 60 mg per day) reduced anxiety and increased speech in 76% of children (age 5 to 14 years) with selective mutism (163). 

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)... 

If the patient has a pre-existing mood disorder, such as depression or anxiety disorder, antidepressant medication may also be prescribed. Studies have shown that the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) and sertraline (Zoloft) are effective in people with bulimia and anorexia. These medications reduce depression by increasing levels of serotonin, a neurotransmitter. 

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. 

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... 

Abene MV, Hamilton JD. Resolution of fear of flying with fluoxetine treatment. J Anxiety Disord 1998 12 599-603. 

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,... 

A 10-year-old boy with ADHD, oppositional defiant disorder, and generalized and separation anxiety disorders started taking OROS methylphenidate 18 mg/day and fluoxetine 10 mg/day. Four days later, he had an acute episode of intense hallucinations 3 hours after taking the medications. His mother reported that the visual hallucinations lasted about 1 hour and the tactile hallucinations more than 2 hours. Two days later he had a similar episode. His mother withdrew the medications for 10 days, during which time he was symptom free. When OROS methylphenidate 18 mg/day monotherapy was restarted he did not report any hallucinations. Mirtazapine 15 mg/day was added for symptoms of anxiety and sleep disturbances. During the next 2 months his condition improved and he had no further hallucinations. 

Corynomycollc acid isolated from the cell walls of Cor-ynebacterium sp. or related organisms exhibit immunostimu-lant properties.Duloxetine is a serotonin-norepinephrine reuptake inhibitor used in major depressive disorder, general anxiety disorder, stress urinary incontinence,diabetic peripheral neuropathy, fibromyalgia,and chronic musculoskeletal pain associated with osteoarthritis and chronic lower back pain. Fluoxetine is a serotonin-uptake inhibitor used as an antidepressant and for treatment of anxiety, alcoholism, and bulimia. " ... 

In 1987, the United States Food and Dmg Administration (FDA) approved the use of fluoxetine for the treatment of depression and this derivative is now considered to be the prototype of a dmg class called selective serotonin reuptake inhibitors (SSRIs). As the name suggests, this term refers to the reuptake blockage of serotonin into the pre-synaptic membrane in order to indirectly increase neurotransmitter availability. A number of these derivatives showed beneficial effects for the treatment of a variety of additional conditions such as obsessive-compulsive disorders (OCD), bulimia nervosa, anxiety disorders, obesity, anorexia, post-traumatic stress disorders (PTSD) and others. SSRIs have become the first-line therapy for depression, which is based on improved side effect profiles when compared with TCA derivatives or MAOIs. A number of adverse effects are described in the pharmacological literature and include sexual dysfunction. 

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. 

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