Venlafaxine & weight gain? The focus of this post is to explore evidence be one of the most common side effects of venlafaxine. Additionally, I will talk about other aspects of venlafaxine, including licensed use, and common side effects.
What is Venlafaxine?
Venlafaxine is an antidepressant drug used to treat major depression, general and social anxiety disorders and panic conditions (BNF, 2021). It was first marketed in 1994 in the UK and is the most commonly used drug of its class of Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs). Despite its popularity, overall, venlafaxine is less prescribed than Selective Receptor Inhibitors (SSRs), like sertraline and citalopram, which are the most commonly used antidepressants in the UK. Read more about the most popular antidepressants in the UK.
Different forms of venlafaxine available in the UK
Venlafaxine is available in UK for oral administration in variety of forms, including (BNF, 2021):
- tablets (37.5mg and 75mg),
- modified-release tablets (37.5mg, 75mg, 150mg, 225mg and 300mg) and
- modified-release capsules (37.5mg, 75mg, 150mg and 225mg)
What is venlafaxine used for?
Main conditions treated with venlafaxine include (ibid);
- Major depression
- Generalized & Social Anxiety Disorder
- Panic Disorder and
- Generalised anxiety disorder and
- Menopausal symptoms, particularly hot flushes, in women with breast cancer
Venlafaxine: mechanism of action
As already discussed, venlafaxine belongs to the class of serotonin and norepinephrine reuptake inhibitors (SNRIs). It works by potentiating (making more ‘active’) the neurotransmitter activity in the central nervous system (brain) and blocks the reuptake or reabsorption of serotonin and norepinephrine, prolonging their actions in the brain. It also weakly inhibits dopamine uptake. This increases the levels of serotonin, norepinephrine and dopamine in the brain. Depression is characterised by disturbance in serotonin, norepinephrine, and dopamine transmission in the brain (Moret & Briley, 2011).
How do antidepressants work?
Venlafaxine vs SSRIs
Venlafaxine is a potent serotonin reuptake inhibitor than a norepinephrine reuptake inhibitor (Singh & Saadabad, 2020). In contrast, commonly prescribed Selective Serotonin Reuptake Inhibitors (SSRIs) in the UK are sertraline, fluoxetine, citalopram, escitalopram, and fluvoxamine, which mainly by increasing serotonin levels (MHRA, 2014). Venlafaxine acts as a Selective serotonin reuptake inhibitor (SSRI) when given at low doses of 75mg/day and with high doses of 225 mg/day; it has a strong norepinephrine reuptake inhibitor activity (Singh & Saadabad, 2020).
When is venlafaxine used for depression?
Many classes of antidepressants are available for treating mild to severe depression, anxiety and panic disorders. Selective serotonin reuptake inhibitors (SSRIs) are considered the first line of choice for treating depression as they are well tolerated and safer even when given in higher doses (1). Fluoxetine and citalopram are considered the most rational choice among SSRIs as they have fewer withdrawal symptoms (NICE, 2007).
If the treatment fails to respond, then 2nd line of choice is to be considered, including Tricyclic antidepressant (TCA) or venlafaxine, especially for a more severe form of depression (BNF, 2021). Overall, venlafaxine is well tolerated than TCAs. It usually causes a dose-related rise in blood pressure, and monitoring is required for uncontrolled blood pressure and impaired cardiac function (Oxford Health Formulary, N.D.).
Venlafaxine is not the first line of treatment for depression and anxiety. Still, it can be considered if a patient cannot tolerate SSRI or treatment fails to respond to other antidepressants. A research study was carried out to determine the effectiveness and safety of switching to venlafaxine or citalopram after failure to respond to SSRI therapy. The aim was to treat patients with moderate to severe depression who have failed to respond to treatment with other selective serotonin reuptake inhibitor. The results regarding efficacy were similar for both citalopram and venlafaxine. Still, the patients with severe depression were found to benefit more from venlafaxine therapy rather than switching to other SSRIs, for example, citalopram (NICE, 2007).
Do all antidepressants cause weight gain?
One of the leading studies which evaluated the long-term impact of antidepressant use on weight gain reviewed the data of 136 762 men and 157 957 women who had three or more records for body mass index (BMI). The primary outcome for this study was to find instances of patients who gained more than 5% of body weight or who transitioned to overweight or obese. This study concluded that the widespread use of antidepressants has led to an increased risk of weight gain and obesity in people (Gafoor et al., 2018).
Weight gain while on therapy with antidepressants can be a positive sign of improvement in patients who have suffered weight loss as a sign of depression or residual symptom of overeating when depressed. However, a significant increase in weight during treatment or continuous weight gain even after achieving remission of depressive symptoms may be the side effect of antidepressants. Tricyclic Antidepressants (TCAs, for example, amitriptyline) and Monoamine Oxidase Inhibitors (MAOIs) have more tendencies to cause weight gain as compared to Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs, for example, Venlafaxine) (Fava, 2000).
Does venlafaxine cause weight gain commonly?
The use of venlafaxine is associated with common side effects. The list of very common and common side effect includes over 30 side effects. Weight change is listed as a common side effect.
Side effects with antidepressants are usually dependent on their long-term use, depression severity and high doses. In a study, venlafaxine showed profuse sweating as the most common side effect after its administration and weight gain was observed more commonly in females’ patients (Bet et al., 2013).
Long term therapy with new-generation antidepressants, including venlafaxine, SSRI and mirtazapine, is associated with weight gain. Generally, 3 to 4 kg of weight gain was observed in 6 to 12 months of therapy (Masand PS, Gupta, 2012).
Another research with the duration of therapy from 6 to 36 months also supported the same results with newer antidepressants, including venlafaxine. The prevalence rate of increase in body weight was 55.2% among 362 patients, with a significant increase of 7% to baseline weight in 40% of patients (Uguz et al., 2015).
A study was conducted to access the tolerability profile of high dose venlafaxine in major depressive disorder patients. 29.6% of patients were presented with complaints of weight gain along with fatigue in 40% of patients as the most common side effect (Harrison et al., 2004).
Research showed the relation between long term antidepressant prescribing and the effect on the weight of the population. The risk of weight gain increases with an increasing year of therapy. Among Serotonin Norepinephrine Reuptake Inhibitors (SNRIs), mirtazapine was associated with significant weight gain, and venlafaxine showed less weight gain than tricyclic antidepressants as Amitriptyline and Selective Serotonin reuptake inhibitors (SSRI) as citalopram, escitalopram, sertraline and fluoxetine (Gafoor et al., 2018).
Venlafaxine – weight gain: conclusion
An increase in weight is associated with the use of antidepressants. While choosing an antidepressant, this factor needs to be considered. Venflaxine is considered superior because of its dual mode of action and effectiveness in terms of safety and tolerance; however, it is not viewed as a first-line treatment to treat depression in the UK.
When considering the treatment for major depression and anxiety disorders, venlafaxine and single-dose prolonged-release Venlafaxine should be given priority compared to SSRIs because both forms of venlafaxine have shown improved efficacy, early onset of action, low risk of drug interactions and less tendency of causing weight gain (ibid). Venlafaxine is found to be equally effective as fluoxetine or paroxetine in treating major depression and has a similar adverse event profile as most SSRIs, but it has an added benefit of being well-tolerated and reducing the symptoms of anxiety in depressive patients, so it should be taken into consideration as the first line of treatment for major depression (Wellington & Perry, 2001).
Bet PM, Hugtenburg JG, Penninx BW, Hoogendijk WJ. Side effects of antidepressants during long-term use in a naturalistic setting. Eur Neuropsychopharmacol. 2013 Nov;23(11):1443-51. doi: 10.1016/j.euroneuro.2013.05.001. Epub 2013 May 30. PMID: 23726508. Available at: https://doi.org/10.1016/j.euroneuro.2013.05.001 Accessed on 31/05/2021
BNF (2021). London: Pharmaceutical Press. Available at: Accessed on 31/05/2021
Fava M. Weight gain and antidepressants. J Clin Psychiatry. 2000;61 Suppl 11:37-41. PMID: 10926053. Available at: https://www.psychiatrist.com/jcp/effects/weight/weight-gain-antidepressants/ Accessed on 31/05/2021
Gafoor R, Booth HP, Gulliford MC (2018). Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population-based cohort study. BMJ. 2018 May 23;361:k1951. doi: 10.1136/bmj.k1951. PMID: 29793997; PMCID: PMC5964332. Available at: https://doi.org/10.1136/bmj.k1951 Accessed on 31/5/2020
Harrison CL, Ferrier N, Young AH (2004). Tolerability of high-dose Venlafaxine in depressed patients. J Psychopharmacol. 2004 Jun;18(2):200-4. doi: 10.1177/0269881104042621. PMID: 15260908. Available at: https://doi.org/10.1177/0269881104042621 Accessed on 31/05/2021
Masand PS, Gupta S (2002). Long-term side effects of newer-generation antidepressants: SSRIs, Venlafaxine, nefazodone, bupropion, and mirtazapine. Ann Clin Psychiatry. 2002 Sep;14(3):175-82. doi: 10.1023/a:1021141404535. PMID: 12585567. Available at: https://doi.org/10.1023/a:1021141404535 Accessed on 31/05/2021
MHRA (2014): Guidance Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs): use and safety. Available at: https://www.gov.uk/government/publications/ssris-and-snris-use-and-safety/selective-serotonin-reuptake-inhibitors-ssris-and-serotonin-and-noradrenaline-reuptake-inhibitors-snris-use-and-safety Accessed on 31/05/2021
Moret C, Briley M (2011). The importance of norepinephrine in depression. Neuropsychiatr Dis Treat. 2011;7(Suppl 1):9-13. doi:10.2147/NDT.S19619 Available at: https://dx.doi.org/10.2147%2FNDT.S19619 Accessed on 28/05/2021
NICE(2007). NICE Clinical guideline 23 Depression; 2007; Available at: https://www.nice.org.uk/guidance/cg23/documents/depression-amendment-nice-guideline-draft-for-consultation2. (Accessed 26.05.2021)
Oxford Health Formulary, NHS (N.D.). Oxford Health Prescribing Guidelines for Depression in Adults. Available at http://www.oxfordhealthformulary.nhs.uk/docs/Oxford%20Health%20Prescribing%20Guidelines%20for%20Depression%20in%20Adults%20(1).pdf. (Accessed 26/05/2021)
Singh D, Saadabadi A (2020). Venlafaxine. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available at: https://www.ncbi.nlm.nih.gov/books/NBK535363/ Accessed 31/05/2021
Wellington K, Perry CM. Venlafaxine extended-release: a review of its use in the management of major depression. CNS Drugs. 2001;15(8):643-69. doi: 10.2165/00023210-200115080-00007. PMID: 11524036.
Uguz F, Sahingoz M, Gungor B, Aksoy F, Askin R (2015). Weight gain and associated factors in patients using newer antidepressant drugs. Gen Hosp Psychiatry. 2015 Jan-Feb;37(1):46-8. doi: 10.1016/j.genhosppsych.2014.10.011. Epub 2014 Oct 31. PMID: 25467076. Available at: https://doi.org/10.1016/j.genhosppsych.2014.10.011 Accessed on 31/05/2021
Wellington K, Perry CM (2001). Venlafaxine extended-release: a review of its use in the management of major depression. CNS Drugs. 2001;15(8):643-69. doi: 10.2165/00023210-200115080-00007. PMID: 11524036. Available at: https://doi.org/10.2165/00023210-200115080-00007 Accessed on 31/05/2021