Depression Symptoms Treatment

Uses and Administration

Prevention of the reuptake of monoamine transmitters such as serotonin, which potentiates their action in the brain, appears to be associated with antidepressant activity. SSRIs such as fluoxetine preferentially inhibit the reuptake of serotonin compared with noradrenaline, and have limited direct action at other neurotrans-mitter sites, including muscarinic receptors. They therefore cause fewer antimuscarinic or sedative adverse effects than the tricyclic antidepressants and are less cardiotoxic. Citalopram is the most selective of the SSRIs currently available, whereas paroxetine is the most potent.

SSRIs provide an alternative to the tricyclics for the treatment of depression. As with the tricyclics, it may be several weeks before an antidepressant effect is seen. Once depression has then resolved, maintenance therapy should be continued for at least 4 to 6 months (12 months in the elderly) to avoid relapse on stopping therapy. Patients with a history of recurrent depression should continue to receive maintenance treatment for at least 5 years and possibly indefinitely.

Some SSRIs are also used as part of the management of generalised anxiety disorder, obsessive-compulsive disorder, panic disorders with or without agoraphobia, social phobia, and post-traumatic stress disorder, and as part of the management of bulimia nervosa. Fluoxetine is also used in the treatment of premenstrual dys-phoric disorder.

Fluoxetine, a phenylpropylamine derivative, is given orally as the hydrochloride doses are expressed in terms of the base. Fluoxetine hydrochloride 22.4 mg is equivalent to about 20 mg of fluoxetine.

In the treatment of depression the usual initial dose of fluoxetine is 20 mg once daily US product information recommends giving this dose in the morning. If no clinical response is seen after several weeks, the daily dose may be gradually increased, up to a maximum of 80 mg daily (60 mg in the elderly). Doses above 20 mg daily may be given in 2 divided doses, for example in the morning and at noon, or as a once daily dose. A once-weekly, modified-release preparation equivalent to 90 mg of fluoxetine is available in the USA for use in patients whose depressive symptoms have stabilised, and who require long-term treatment it is recommended that weekly dosing is started 7 days after the last daily dose of fluoxetine.

Fluoxetine is also used for the treatment of depression in children aged 8 years and over. Initial doses of 10 mg should be increased to 20 mg daily after 1 week (except in low-weight children when such increases should not be made for several weeks, and then only if the clinical response is insufficient). Because of concerns about the use of SSRIs in children (see Effects on Mental State, above) its use is licensed in the European Union only as an adjunct to psychological therapy in children and adolescents with moderate to severe depression who have not responded to psychological therapy alone.

Fluoxetine is used in recommended doses of 60 mg once daily in the management of bulimia nervosa. In the management of obsessive-compulsive disorder the initial dose of fluoxetine is 20 mg once daily increased after several weeks if there is no response to up to 60 mg daily. Up to 80 mg daily has been used, sometimes divided into 2 doses. Fluoxetine is also licensed in the USA for use in children aged 7 years and over for obsessive-compulsive disorder. The starting dose is 10 mg daily in low-weight children this is increased after several weeks to 20 to 30 mg daily, if required. Adolescents and heavier children may be increased to 20 mg daily after 2 weeks further increases to 60 mg daily may be made after several weeks, as necessary.

Fluoxetine may be used in the treatment of panic disorder in initial doses of 10 mg once daily. After a week the dose should be increased to 20 mg daily further increases to 60 mg daily may be considered after several weeks if no improvement is seen.

A dose of 20 mg daily is used in the treatment of premenstrual dysphoric disorder. Intermittent dosing is also permitted: for each new cycle, fluoxetine should be started 14 days before the onset of menstruation and continued until the first full day of menstruation. Treatment may be continued for 6 months benefit should then be reassessed before continuing further.

A lower or less frequent dosage is recommended in elderly patients. For dosage in hepatic or renal impairment see below.

It should be noted that because fluoxetine and nor-fluoxetine have prolonged half-lives several weeks of therapy are required before steady-state concentrations are attained similarly after dosage adjustments a time lag will occur before steady-state concentrations are again achieved. Although SSRIs should generally be withdrawn gradually to reduce the risk of withdrawal symptoms, the long half-life may reduce the need for dose tapering with fluoxetine.

Administration in hepatic or renal impairment. Fluoxetine is subject to hepatic metabolism, and, therefore, lower doses, such as alternate-day dosing, have been recommended in patients with significant hepatic impairment.

It is also excreted by the kidneys and licensed information for some UK products recommends a similar dose reduction in patients with mild to moderate renal impairment and that fluoxetine should be avoided in those with severe impairment. However, other UK and US product information states that plasma concentrations of fluoxetine or its metabolite norfluoxetine in patients with severe impairment requiring dialysis did not differ from those in controls with normal renal function when given fluoxetine 20 mg daily for 2 months.

Anorexia nervosa. Counselling and psychotherapy form the major part of treatment of anorexia nervosa and there is little or no role for specific drug therapy. Antidepressants may be indicated when there is co-existing depression or obsessive-compulsive disorder but malnourished anorexic patients may be more susceptible to adverse effects and less responsive than other patients with depression. Fluoxetine has been tried with some success particularly when used to prevent relapse once weight gain has been achieved.

Anxiety disorders. SSRIs have been given in a variety of anxiety disorders but their role in these disorders is most well established in the treatment of obsessive-compulsive disorder. Efficacy in obsessive-compulsive disorder appears to have been best demonstrated for fluvoxamine and fluoxetine but other SSRIs are also effective and patients unresponsive to one SSRI may respond to another. SSRIs are also of use in the treatment of generalised anxiety disorder, panic disorder, and post-traumatic stress disorder. SSRIs are considered to be the first choice for the treatment of social anxiety disorder (see under Phobic Disorders). Fluoxetine is one of the SSRIs that has been tried in the treatment of trichotillomania.

Bipolar disorder. Treatment of the depressive phase of bipolar disorder with antidepressants needs caution since these drugs may precipitate mania or hypomania. SSRIs such as fluoxetine have nonetheless been used in bipolar disorder with some success. In some countries, fluoxetine is also available as a fixed-dose combination with the atypical antipsychotic olanzapine for use in the depressive phase of bipolar disorder.

Bulimia nervosa. A combination of counselling, support, psychotherapy, and antidepressants is the usual treatment for bulimia nervosa. Fluoxetine and the tricyclic desipramine have been suggested as the antidepressants of choice because they have been used extensively and are considered to be well tolerated. Other S SRIs that have been tried include sertraline, fluvoxamine, and paroxetine. Antidepressants in general do not appear to alter the patient’s disturbed self-image, although disturbed attitudes might improve during short-term therapy with fluoxetine. References.

Depression. As discussed, there is very little difference in efficacy between the different groups of antidepressant drugs, and choice is often made on the basis of adverse effect profile. SSRIs such as fluoxetine are widely used as an alternative to the older tricyclics as they have fewer adverse effects and are safer in overdosage.

Combination therapy with differing classes of antidepressants, including the SSRIs, has been used in the treatment of drug-resistant depression. However, such therapy may result in enhanced adverse reactions or interactions and is considered unsuitable or controversial by some workers. For further details see Antidepressants, under Interactions of Phenelzine. References to the use of SSRIs in general and to the use of fluoxetine are given below.

Disturbed behaviour. SSRIs appear to have been of some benefit in controlling symptoms such as impulsiveness and aggression when tried in various disorders for the management of disturbed behaviour. There have been several case reports of fluoxetine being used with some success in the control of fantasies associated with various paraphilias.

Headache. The results of several studies have suggested that SSRIs may be of benefit in the treatment of chronic tension-type headache however, results in the prophylaxis of migraine have been conflicting. References.

Hot flushes. HRT with oestrogens is usually the mainstay of acute treatment for symptoms such as hot flushes associated with the menopause however, HRT has potentially tumour-stimulating effects and may be unsuitable in some patients, particularly those with a history of breast cancer (see Malignant Neoplasms, under Precautions of HRT). Preliminary studies have shown that some SSRIs (fluoxetine, paroxetine, and sertraline) have a modest effect on alleviating hot flushes and may be an alternative to HRT in peri- and postmenopausal women and in women with a history of breast cancer. However, there is some concern that the SSRI paroxetine may interact with tamoxifen treatment in patients with breast cancer (see Antidepressants under Interactions in Tamoxifen). In addition, paroxetine has been tried in the treatment of hot flushes in men receiving anti-androgen therapy for prostate cancer.

The serotonergic antidepressant venlafaxine has also been tried with some success in men and women with hot flushes in whom other treatments were unsuitable.

Hyperactivity. When drug therapy is indicated for attention deficit hyperactivity disorder (ADHD) initial treatment is usually with a central stimulant. SSRIs such as fluoxetine have produced beneficial effects as an adjunct to central stimulants in small numbers of patients with comorbid disorders such as depression or obsessive-compulsive disorder although there is insufficient evidence to assess their efficacy in ADHD alone.

Hypochondriasis. SSRIs may be of benefit in patients with hypochondriasis. Fluoxetine in an initial dose of 20 mg daily gradually increased up to 80 mg daily produced some beneficial results in 10 of 14 patients with hypochondriasis who completed 12 weeks of treatment. Fluvoxamine and paroxetine have also been tried.

Hypotension. SSRIs have been used in patients with neurally mediated hypotension refractory to standard treatment, although evidence of benefit is mainly anecdotal. However, a small study found that paroxetine reduced the incidence of both tilt-induced and spontaneous syncope. See also Orthostatic Hypotension, below.

Obesity. Fluoxetine has been tried with some success as part of the management of obesity. Fluoxetine’s mechanism of action in obesity is unknown. Serotonin is believed to be involved in the regulation of satiety but fluoxetine has also been shown to increase resting energy expenditure and raise basal body temperature. A common dose for fluoxetine in the management of obesity has been 60 mg daily it appears that fluoxetine has a dose-related effect on weight loss. Reviews agree that fluoxetine can aid weight reduction in the short term but after 16 to 20 weeks some patients have started to regain weight and its long-term efficacy remains to be established. Troublesome adverse effects can occur. Some patients treated with fluoxetine for depression have experienced an increase of appetite and some have gained weight. There has been a report of a patient who lost weight during treatment with fluoxetine for depression despite an increased appetite and food intake.

Orthostatic hypotension. Although orthostatic hypotension has been reported in some patients taking SSRIs, there has been a report that fluoxetine 20 mg daily for 6 to 8 weeks produced beneficial effects in 4 of 5 patients with chronic symptomatic orthostatic hypotension refractory to other treatment. Modest benefits have also been seen in patients with orthostatic hypotension associated with parkinsonism.

Pain. SSRIs have been tried in the treatment of painful disorders including fibromyalgia and diabetic neuropathy. See also Headache, above.

Parkinsonism. It has been suggested that fluoxetine might be of use in the management of selected patients with Parkinson’s disease who have levodopa-induced dyskinesias unresponsive to other measures. However, although fluoxetine has been reported to have produced beneficial results in such patients there has also been a report of increased disability in patients with Parkinson’s disease given fluoxetine. Extrapyramidal effects have also been reported in other patients taking fluoxetine (see under Adverse Effects, above). Fluoxetine has been tried in parkinsonism-related orthostatic hypotension (above).

Pathological crying or laughing. Inappropriate or uncontrolled crying or laughing can occur in patients with lesions in certain areas of the brain. Attempts at treatment have mostly been with antidepressant drugs, including SSRIs. Beneficial effects have been claimed for fluoxetine in a number of uncontrolled studies and reports.

Peripheral vascular disease. Anecdotal reports’ and a small pilot study of fluoxetine (in a daily dose of 20 to 60 mg) suggest it may produce favourable therapeutic responses in patients with Raynaud’s syndrome (see Vasospastic Arterial Disorders).

Premenstrual syndrome. Fluoxetine is used to control both the psychological and somatic symptoms of women with premenstrual dysphoric syndrome, a severe form of premenstrual syndrome. Other SSRIs also appear to be useful, although evidence is so far more limited.

Sexual dysfunction. Impotence or ejaculatory problems have been reported as adverse effects of SSRIs (see Effects on Sexual Function in Adverse Effects, above). Such properties of the SSRIs have been studied as a potential form of treatment for men with premature ejaculation. The relative effects of the SSRIs on delaying ejaculation have also been studied Paroxetine was found to cause the strongest delay, followed by fluoxetine and then sertraline fluvoxamine caused a slight delay although the effect was not significantly different from that seen with placebo. (Citalopram was unavailable at the time of the study later studies of its effect have been conflicting.)

Preparations

BP 2008: Fluoxetine Capsules Fluoxetine Oral Solution

The United States Pharmacopeia 31, 2008: Fluoxetine Capsules Fluoxetine Delayed-Re I ease Capsules Fluoxetine Oral Solution Fluoxetine Tablets.

Proprietary Preparations

Argentina: Alental Animex-On Anzolden Captaton Eburnate Equilibrane Faboxetina Felixina Fibrotina Fluopiram Foxetin Lapsus Mitilase Nervosal Neupax Neuro Laz Prozac Saurat

Australia: Auscap Erocap † Fluohexal Fluoxebell Lovan Prozac Zactin

Austria: Felicium Fluctine Fluoxenorm Fluoxibene Fluoxistad Fluxil FluxoMed Mutan NuFluo Positivum

Belgium: Docfluoxetine Fluox Fluoxemed Fluoxone Fontex Prosimed Prozac

Brazil: Daforin Deprax Depress Eufor Fluox Fluxene Nortec Prozac Frozen Psiquial Verotina

Canada: FXT Prozac

Chile: Actan Alentol Anisimol Clinium Dominium Pragmaten Prozac Sostac Tremafarm †

Czech Republic: Deprenon † Deprex Floxet Flumirex † Fluocim † Fluogal Fluoxin Fluval Fluxonil † Fluzak Framex † Magrilan Milezin † Portal Prozac

Denmark: Afeksin Flutin Fluxantin Folizol Fondur † Fonigen † Fontex Fonzac

Finland: Fluoxal † Fluxantin † Fontex † Seromex Seronil

France: Prozac

Germany: Fluctin Fluneurin Fluox Fluox-Puren Fluoxa † Fluoxe-Q FluoxeLich Fluoxemerck † Fluoxgamma Fluxet Fysionorm †

Greece: Dagrilan Dinalexin Exostrept Flonital Fluocalm Fluxadir Fokeston FHapilux Ladose Orthon Sartuzin Sofelin Stephadilat-S Stressless Thiramil Zinovat

Hong Kong: Atd CP-Fluoxet Deprexin Fluxetin Fluxil Magrilan † Nopres Plazeron † Provatine † Prozac Qualisac

Hungary: Deprexin Fefluzin † Floxet FluWinox Portal Prozac

India: Depzac Fludac Flufran † Nuzac Platin

Ireland: Affex Biozac Gerozac Norzac Prozac Prozamel Prozatan Prozit

Israel: Affectine Flutine Prizma Prozac

Italy: Azur Clexiclor Cloriflox Deprexen Diesan Flotina Fluoxeren Fluoxin Grinflux † Ibixetin † Ipsumor Prozac Serezac † Xeredien Zafluox †

Malaysia: Fluran Fluxetil Prozac Salipax

Mexico: Aponeusak Auroken † Axtin Deprozin Farmaxetina Flocet Florexal Fluctine Fluneurin Fluoxac Fluralex Flutinax Indozul Lebensart Ovisen Prozac Quanilene Regultron Siquial Ulmely Zatin

The Netherlands: Fluoxstad Flustad Prozac

Norway: Fontex

New Zealand: Fluox Plinzene Prozac

Philippines: Adepssir Deprexone Deprizac Prozac

Poland: Andepin Bioxetin Deprexetin Salipax Seronil

Portugal: Digassim Mizac † Nodepef Prozac Psipax Salipax Selectus Tuneluz

Russia: Apo-Fluoxetine Fluval Framex Portal Prodep Proflusak Prozac

South Africa: Deprozan Lorien Nuzak Prohexal Prozac Ranflocs Sanzur †

Singapore: Deprexin Fluxetil Fluxetin Fluxil Foxtin Nagrilan Prozac Zactin

Spain: Adofen Astrin † Augort † Ledmar Luramon Nodepe Prozac Reneuron Zaxetina †

Sweden: Fluxantin † Fontex Seroscand †

Switzerland: Fluctine Fluesco Fluocim Fluoxbasan † Fluoxifar Flusol

Thailand: Actisac † Anzac Dawnex Deproxin Flulox Flurried Fluoxine Flusac Flutine Fluxetil Fluxetin Fluzac Hapilux † Loxetine Nagrilan Oxetine Oxsac Prodep Prozac Unprozy

Turkey: Depreks Fulsac Loksetin Prozac Seronil Zedprex

United Arab Emirates: Flutin

UK: Prozac Prozit

USA: Prozac Sarafem

Venezuela: Anoxen Antipres Fluxet Fluzac Prozac Psiquial

Multi-ingredient

Argentina: Combined Symbyax †

Chile: Symbyax

India: Fludep Plus

Mexico: Symbyax

USA: Symbyax