Fluvoxamine, sold under the brand name Luvox among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is primarily used to treat major depressive disorder and, perhaps more especially, obsessive–compulsive disorder (OCD), but is also used to treat anxiety disorders such as panic disorder, social anxiety disorder, and post-traumatic stress disorder.
Fluvoxamine's side-effect profile is similar to that of other SSRIs. Common adverse effects include constipation, gastrointestinal problems, headache, anxiety, irritation, sexual problems, dry mouth, sleep problems, and an increased risk of suicide at the start of treatment. These effects appear to be significantly weaker than with other SSRIs, with the exception of gastrointestinal side-effects. In some patients, sexual dysfunction may persist even after the drug is discontinued, a condition known as post-SSRI sexual dysfunction; regulatory agencies including the European Medicines Agency and Health Canada have recommended that fluvoxamine's product labeling warn of this risk.
Fluvoxamine appears to be more tolerable than other SSRIs, particularly with respect to cardiovascular complications.
It is on the World Health Organization's List of Essential Medicines.
Medical uses
In many countries (e.g., Australia, the United Kingdom, and Russia) it is commonly used for major depressive disorder. Fluvoxamine is also approved in the United States for obsessive–compulsive disorder (OCD), and social anxiety disorder. In Japan, it is also approved to treat OCD, social anxiety disorder, and major depressive disorder. Fluvoxamine is indicated for children and adolescents with OCD. The NICE guidelines in the United Kingdom have, as of 2005, authorized its use for OCD in adults and adolescents of any age and children over the age of 7.
There is evidence that fluvoxamine is effective for generalised social anxiety in adults, although, as with other SSRIs, some of the results may be compromised by having been funded by pharmaceutical companies. Of the SSRIs, however, fluvoxamine, paroxetine, and sertraline do appear consistent as viable treatments for generalised social anxiety.Williams, T., McCaul, M., Schwarzer, G., Cipriani, A., Stein, D. J., & Ipser, J. (2020). Pharmacological treatments for social anxiety disorder in adults: a systematic review and network meta-analysis. Acta neuropsychiatrica, 32(4), 169–176. https://doi.org/10.1017/neu.2020.6 Davidson J. R. (2003). Pharmacotherapy of social phobia. Acta psychiatrica Scandinavica. Supplementum, (417), 65–71. https://doi.org/10.1034/j.1600-0447.108.s417.7.x
Fluvoxamine is also effective for treating a range of anxiety disorders in children and adolescents, including generalized anxiety disorder, social anxiety disorder, panic disorder, and separation anxiety disorder.
The drug works long-term, and retains its therapeutic efficacy for at least one year.
The average therapeutic dose for fluvoxamine is 100 to 300 mg/day, with 300 mg being the upper daily limit normally recommended. OCD, however, often requires higher doses; doses of up to 450 mg/day may be prescribed in this case.Seibell PJ, Hamblin RJ, Hollander E.
Obsessive-compulsive disorder: Overview and standard treatment strategies. Psychiatric Annals. 2015 Jun 1;45(6):297-302.Rivas-Vazquez, R.A., and Blais, M.A., 1997. Selective serotonin reuptake inhibitors and atypical antidepressants: A review and update for psychologists. Professional Psychology: Research and Practice, 28(6), p.526.Middleton, R., Wheaton, M.G., Kayser, R., and Simpson, H.B., 2019. Treatment resistance in obsessive-compulsive disorder. Treatment resistance in psychiatry: risk factors, biology, and management, pp.165-177. The (off-label) upper daily limits for other serotonin-reuptake inhibitors used in the treatment of OCD, by analogy, are 400 mg for sertraline,Ninan PT, Koran LM, Kiev A, Davidson JR, Rasmussen SA, Zajecka JM, Robinson DG, Crits-Christoph P, Mandel FS, Austin C. High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial. J Clin Psychiatry. 2006 Jan;67(1):15-22. doi: 10.4088/jcp.v67n0103. PMID 16426083. 100 mg for paroxetine, 120 mg for both fluoxetine and citalopram, 60 mg for escitalopram and 300 mg for clomipramine.Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB; American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007 Jul;164(7 Suppl):5-53. PMID 17849776.
In any case with fluvoxamine, treatment is generally begun at 50 mg and increased in 50 mg increments every 4 to 7 days until a therapeutic optimum is reached.Figgitt, D.P., and McClellan, K.J., 2000. Fluvoxamine: an updated review of its use in the management of adults with anxiety disorders. Drugs, 60, pp.925-954.
Adverse effects Fluvoxamine's side-effect profile is very similar to other SSRIs. Gastrointestinal side effects are characteristic of those receiving treatment with fluvoxamine. However, compared to escitalopram and sertraline, fluvoxamine's gastrointestinal profile may be less intense, often being limited to nausea. Mosapride has demonstrated efficacy in treating fluvoxamine-induced nausea. It is also advised practice to divide total daily doses of fluvoxamine greater than 100 mg, with the higher fraction being taken in the evening (e.g., 50 mg at the beginning of the waking day and 200 mg at bedtime). In any case, high starting daily doses of fluvoxamine rather than the recommended gradual titration (starting at 50 mg and gradually titrating, up to 300 mg if necessary) may increase the likelihood of nausea.
In comparison to other SSRIs, fluvoxamine has the second highest rate of causing discontinuation syndrome, as a result of the low half-life of fluvoxamine.
Common
Common side effects occurring with 1–10% incidence:
Abdominal pain Agitation Anxiety Asthenia (weakness) Constipation Diarrhea Dizziness Dyspepsia (indigestion) Headache Hyperhidrosis (excess sweating) Insomnia Loss of appetite Malaise Nausea Nervousness Palpitations Restlessness Sexual dysfunction (including delayed ejaculation, erectile dysfunction, decreased libido, etc.) Somnolence (drowsiness) Tachycardia (high heart rate) Tremor Vomiting Weight loss Xerostomia (dry mouth) Yawning
Uncommon
Uncommon side effects occurring with 0.1–1% incidence:
Arthralgia Confusional state Cutaneous hypersensitivity reactions (e.g. oedema [buildup of fluid in the tissues], rash, pruritus) Extrapyramidal side effects (e.g. dystonia, parkinsonism, tremor, etc.) Hallucination Orthostatic hypotension
Rare
Rare side effects occurring with 0.01–0.1% incidence:
Abnormal hepatic (liver) function Galactorrhoea (expulsion of breast milk unrelated to pregnancy or breastfeeding) Mania Photosensitivity (being abnormally sensitive to light) Seizures
Unknown frequency
Akathisia a sense of inner restlessness that presents itself with the inability to stay still Bed-wetting Bone fractures Dysgeusia Ecchymoses Glaucoma Haemorrhage Hyperprolactinaemia (elevated plasma prolactin levels leading to galactorrhoea, amenorrhoea [cessation of menstrual cycles], etc.) Hyponatraemia Mydriasis Neuroleptic malignant syndrome – practically identical presentation to serotonin syndrome except with a more prolonged onset Paraesthesia Serotonin syndrome – a potentially fatal condition characterised by abrupt onset muscle rigidity, hyperthermia (elevated body temperature), rhabdomyolysis, mental status changes (e.g. coma, hallucinations, agitation), etc. Suicidal ideation and behaviour Syndrome of inappropriate antidiuretic hormone secretion Urinary incontinence Urinary retention Violence toward others Weight changes Withdrawal symptoms
Post-SSRI sexual dysfunction
Post-SSRI sexual dysfunction (PSSD) is an iatrogenic condition in which sexual side effects persist after discontinuation of serotonin reuptake inhibiting antidepressants, including fluvoxamine. Characteristic symptoms include genital numbness, pleasureless or weak orgasm, loss of libido, and erectile dysfunction; non-sexual symptoms such as emotional blunting and cognitive impairment may also occur. The condition can arise after even brief exposure to a serotonin reuptake inhibitor and may persist indefinitely; there is currently no established treatment. The DSM-5 noted in 2013 that serotonin reuptake inhibitor-induced sexual dysfunction may persist after the agent is discontinued.
A 2023 retrospective cohort study of over 12,000 males estimated the risk of irreversible sexual dysfunction at approximately 0.46% of patients treated with serotonergic antidepressants, including SSRIs, though the actual prevalence remains uncertain and the condition is likely underreported. A 2023 systematic review noted that while data on fluvoxamine is more limited than for some other SSRIs, it was included in the EMA's class-wide signal assessment and cases have been reported with SNRIs, SRI tricyclic antidepressants, and other serotonin reuptake inhibiting drugs in addition to SSRIs. A citizen petition submitted to regulators in 2018 suggested that SNRIs and other serotonin reuptake inhibiting drugs, including fluvoxamine, may be less likely to induce PSSD than SSRIs, though this remains unconfirmed.
In 2019, the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) reviewed evidence on fluvoxamine as part of its class-wide signal assessment and recommended that product labels for all SSRIs and SNRIs be updated to state that sexual dysfunction may be long-lasting even after treatment is stopped. Health Canada followed with similar label updates in 2021. In 2024, Australia's Therapeutic Goods Administration aligned all SSRI and SNRI product information to reflect this risk; fluvoxamine was among the products requiring updated warnings.
Interactions
Fluvoxamine inhibits the following cytochrome P450 enzymes: CYP1A2 (strongly) which metabolizes agomelatine, amitriptyline, caffeine, clomipramine, clozapine, duloxetine, haloperidol, imipramine, phenacetin, tacrine, tamoxifen, theophylline, olanzapine, etc. CYP3A4 (moderately) which metabolizes alprazolam, aripiprazole, clozapine, haloperidol, quetiapine, pimozide, ziprasidone, etc. CYP2D6 (weakly) which metabolizes aripiprazole, chlorpromazine, clozapine, codeine, fluoxetine, haloperidol, olanzapine, oxycodone, paroxetine, perphenazine, pethidine, risperidone, sertraline, thioridazine, zuclopenthixol, etc. CYP2C9 (moderately) which metabolizes nonsteroidal anti-inflammatory drugs, phenytoin, sulfonylureas, etc. CYP2C19 (strongly) which metabolizes clonazepam, diazepam, phenytoin, etc. CYP2B6 (weakly) which metabolizes bupropion, cyclophosphamide, sertraline, tamoxifen, valproate, etc.
By so doing, fluvoxamine can increase serum concentration of the substrates of these enzymes.
Fluvoxamine may also elevate plasma levels of olanzapine by approximately two times. Combined olanzapine and fluvoxamine, which may cause increased sedation, should be used cautiously and controlled clinically and by therapeutic drug monitoring to avoid olanzapine induced adverse effects and/or intoxication.
The plasma levels of oxidatively metabolized benzodiazepines (e.g., triazolam, midazolam, alprazolam, and diazepam) are likely to be increased when co-administered with fluvoxamine. However, the clearance of benzodiazepines metabolized by glucuronidation (e.g., lorazepam; oxazepam, which is coincidentally a metabolite of diazepam; temazepam) are not affected by fluvoxamine and may be safely taken alongside fluvoxamine should concurrent treatment with a benzodiazepine be necessary. Additionally, it appears that benzodiazepines metabolized by nitro-reduction (clonazepam, nitrazepam) may also, in a somewhat similar vein, be unlikely to be affected by fluvoxamine.