Chemical- Fluoxetine Hydrochloride
Adverse Effects- Adverse effects reported with Fluoxetine include
gastro-intestinal disturbances such as nausea, vomiting, dyspepsia,
dry mouth, and diarrhea. Anorexia and weight loss may also occur
although these properties have led to the indication for fluoxetine's
use in bulimia nervosa. Neurological side-effects have included either
anxiety, nervousness, and insomnia or drowsiness and fatigue-
headache, tremor, dizziness, convulsions, and decreased libido have
also occurred. Excessive sweating and pruritus or skin rashes such as
urticaria have also been reported. In some patients with rashes,
systemic events involving the lungs, kidneys, or liver, and possibly
related to vasculitis, have developed- it has therefore been advised
that Fluoxetine therapy should be discontinued in any patient who
develops a skin rash. In overdosage nausea, vomiting, and excitation
of the central nervous system are considered to be prominent features-
death has been reported. Treatment involves emesis induction or
gastric lavage followed by symptomatic and supportive therapy. Forced
diuresis, dialysis, haemoperfusion, and exchange transfusion are
considered unlikely to be of benefit. Effects on Mental State-
Although there have been allegations concerning the ability of
Fluoxetine to increase suicidal ideation, meta-analysis, (1) opinion,
(2) and experience (3) indicate that there is no such increased risk.
However, it has been said that it is not known whether Fluoxetine can
increase hostility or aggression.
(prescription not required)
1. Beasley CM, et al. Fluoxetine and suicide: a meta-analysis of
controlled trials of treatment for depression. Br Med J 1991- 303:
2. Anonymous. Fluoxetine, suicide and aggression. Drug Ther Bull 1992-
3. Committee on Safety of Medicines. Safety of Fluoxetine (Prozac):
comparison with fluvoxamine (Faverin). Current Problems 34 1992.
Epileptogenic Effect- References.
1. Weber JJ. Seizure activity associated with Fluoxetine therapy. Clin
Pharm 1989- 8: 296-8.
2. Ware MR, Stewart RB. Seizures associated with Fluoxetine therapy.
DICP Ann Pharmacother 1989- 23: 428.
Precautions- As Fluoxetine undergoes hepatic
metabolism and renal excretion it should be used with caution and in
reduced doses in patients with impaired hepatic or renal function (see
below under Uses and Administration). Because of its epileptogenic
effect it should be used with caution in patients with epilepsy or a
history of such disorders. Fluoxetine may alter glycemia control and
therefore caution is also warranted in diabetic subjects. Depressed
patients with suicidal tendencies should be carefully supervised
during treatment. Fluoxetine is not usually considered a suitable form
of therapy for the depressive component of bipolar (manic-depressive)
illness as mania may be precipitated. Fluoxetine should be
discontinued in patients who develop a rash since systemic effects,
possibly related to vasculitis, have occurred in such patients.
Interactions have occurred between Fluoxetine and other
antidepressants. Enhancement of the serotonergic effects resulting in
the serotonin syndrome has been reported in patients receiving
Fluoxetine and monoamine oxidase inhibitors concurrently or within a
short interval of each other (see below). Consequently at least 14
days should elapse between discontinuation of a monoamine oxidase
inhibiting antidepressant and the introduction of Fluoxetine. Because
of the long half-lives of Fluoxetine and its metabolite, norfluoxetine,
it is also advised that at least 5 weeks should elapse between
discontinuation of Fluoxetine and the introduction of a monoamine
oxidase inhibitor. Enhancement of the serotonergic effects may also
occur if Fluoxetine is given with Tryptophan or lithium (see below).
There have also been reports of Fluoxetine causing both increased and
decreased concentrations of lithium. Increases in previously stable
concentrations of other antidepressants have also been stated to have
occurred when Fluoxetine was added to the therapy. Interactions- In
the UK the CSM has warned (1) that enhanced serotonergic effects may
result from combination therapy of highly selective serotonin
re-uptake inhibitors, such as Fluoxetine and fluvoxamine, with other
antidepressants, including monoamine oxidase inhibitors, lithium, or
Tryptophan. Although such an enhancement may be beneficial in some
instances it can produce a life-threatening serotonin syndrome
comprising hypothermia, tremor, and convulsions. Indeed, such fatal
effects have been reported in a patient receiving Fluoxetine,
tranylcypromine, and Tryptophan along with other multiple drug
1. Committee on Safety of Medicines. Fluvoxamine and Fluoxetine-interaction
with monoamine oxidase inhibitors, lithium and Tryptophan. Current
Problems 26 1989. (Correction stating that hypothermia should have
read hypothermia. Current Problems 27 1989).
2. Kline SS, et al. Serotonin syndrome versus neuroleptic malignant
syndrome as a cause of death. Clin Pharm 1989- 8:
Use and Administration- Fluoxetine is an
antidepressant. It selectively inhibits the re-uptake of serotonin but
has relatively little effect on noradrenaline re-uptake. It is
reported to cause fewer antimuscarinic side effects than tricyclic
antidepressants. Its mode of action in depression is not fully
understood. In the treatment of depression Fluoxetine is given by
mouth as Fluoxetine hydrochloride. In the UK doses and strengths are
expressed in terms of Fluoxetine hydrochloride whereas in the USA they
are expressed in terms of Fluoxetine. The usual dose of Fluoxetine or
the hydrochloride is 20 mg daily- doses of up to 80 mg daily in
divided doses may be employed if necessary. A recommended maximum dose
for elderly patients is 60 mg daily. Because Fluoxetine is subject to
hepatic metabolism, lower doses, such as alternate-day dosing, have
been recommended in patients with significant hepatic impairment.
Similar recommendations, because of renal excretion, have been made
for patients with mild to moderate renal failure (where the glomerular
filtration-rate is 10 to 50 ml per minute)- it should not, however, be
used at all in patients with severe renal failure (glomerular
filtration-rate of less than 10 ml per minute). It should be noted
that the prolonged half-lives of Fluoxetine and norfluoxetine will
result in the need for several weeks of therapy to be employed before
steady-state concentrations are attained- similarly after dosage
adjustments a time lag will occur before steady-state concentrations
are again achieved. Fluoxetine is also used in doses of 60 mg daily in
the management of bulimia nervosa.
Some general references.
1. Anonymous. Fluoxetine: another new antidepressive. Drug Ther Bull
1990- 28: 33-4.
2. Anonymous. 5-HT blockers and all that. Lancet 1990- 336:
3. Anonymous. Fluoxetine (Prozac) revisited. Med Lett Drugs Ther 1990-
32: 83-5. Like many other antidepressants, the use of Fluoxetine has
been investigated in a variety of disorders in addition to depression.
Beneficial responses have been reported in obsessive compulsive
disorders, (1-3) pain syndromes including diabetic neuropathy (4) and
fibrosis, (5) panic disorders, (6) sleep disorders such as narcolepsy
and cataplexy, (7) and bulimia nervosa. (8)
For mention of the use of Fluoxetine in cataplexy
and sleep paralysis associated with narcolepsy, see Amitriptyline,
1. Turner SM, et al. Fluoxetine treatment of
obsessive-compulsive disorder. J Clin Psychopharmacol 1985- 5:
2. Fontaine R, Chouinard G. An open clinical trial of Fluoxetine in
the treatment of obsessive-compulsive disorder. J Clin Psychopharmacol
3. Granet RB. Fluoxetine treatment of obsessive compulsive disorder. J
Clin Psychiatry 1989- 50: 436.
4. Theesen KA, Marsh WR. Relief of diabetic neuropathy with Fluoxetine.
DICP Ann Pharmacother 1989- 23: 572-4.
5. Geller SA. Treatment of fibrosis with Fluoxetine hydrochloride
(Prozac). Am J Med 1989- 87: 594-5
6. Schneier FR, et al. Fluoxetine in panic disorder. J Clin
Psychopharmacol 1990- 10: 119-21.
7. Langdon N, et al. Fluoxetine in the treatment of cataplexy. Sleep
1986- 9: 371-3.
8. Ramirez LC, et al. Effective treatment of bulimia with
Fluoxetine, a serotonin reuptake inhibitor, in a patient with type I
diabetes mellitus. Am J Med 1990- 88: 540-1.