Effexor (Venlafaxine) For Hot Flashes: A Non-Hormonal Therapy

Effexor (Venlafaxine) is a medication that was originally approved by the FDA in 1993 for the treatment of major depression.  Upon ingestion, Effexor functions as an SNRI (or dual-reuptake inhibitor) by inhibiting the reuptake of serotonin, and to a lesser extent, norepinephrine.  As a result of serotonergic and noradrenergic reuptake inhibition, concentrations of serotonin and norepinephrine increase within the synaptic cleft, allowing for improvements in neuronal communication.

Although clinically approved for the treatment of depression, Effexor is also commonly prescribed as a non-hormonal treatment for hot flashes.  A hot flash is referred to as a brief or sudden onset of heat, often accompanied by facial redness, flushing, and sweating.  The exact physiological underpinnings of hot flashes aren’t well-understood, but a cooling of blood vessels near the surface of the skin and/or changes in circulation are known to occur during a hot flash.

Hot flashes have been linked to a barrage of things including: allergies, chemotherapy, emotional stress, genetic abnormalities, hormone levels, menopause, perimenopause, pharmaceutical drugs, spicy foods, etc.  Regardless of the condition associated with the hot flashes, a root cause may be abnormal neurotransmission within the hypothalamus, which in turn causes thermoregulatory dysfunction to trigger a hot flash.  Administration of Effexor is thought to correct abnormal hypothalamic neurotransmission, thereby restoring normalcy of thermoregulation and decreasing occurrence of hot flashes.

How Effexor May Treat Hot Flashes (Mechanism of Action)

Despite Effexor’s ability to modulate the neurotransmission of monoamines to alter mood, it is unclear how this monoaminergic modulation reduces propensity to experience hot flashes.  Most medical professionals simply tell patients that there is strong evidence to support the efficacy of Effexor as an intervention for hot flashes, but they cannot sufficiently explain how it works.  That said, some scientists have attempted to decipher the mechanisms by which Effexor treats hot flashes.

Hypothalamic modulation: Neurotransmitter concentrations within a region of the brain known as the hypothalamus are believed to influence the likelihood of hot flashes.  When neurotransmission within the hypothalamus is imbalanced (or suboptimal), it induces dysfunction in thermoregulation, which in turn may lead to a hot flash.  Particularly, there appears to be a correlation between density of 5-HT (serotonin) receptors in the hypothalamus and hot flashes.

High concentrations of 5-HT receptors within the hypothalamus tend to alter the body’s thermoregulatory processes from homeostatic baseline, increasing a person’s susceptibility to experience hot flashes.  Upon administration of Effexor, extracellular concentrations of serotonin increase to a significant extent.  These increases in serotonin as induced by the Effexor are thought to facilitate desensitization and/or downregulation of hypothalamic 5-HT receptors.

Downregulation of 5-HT receptors within the hypothalamus recalibrates thermoregulatory processes back to homeostasis and decreases the occurrence of hot flashes.  Alterations in serotonergic transmission within the hypothalamus is likely the primary mechanism by which Effexor reduces hot flashes.  That said, there may be other neurophysiological alterations as induced by Effexor that also contribute to a reduction in hot flashes.

• Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870169/
• Source: http://www.ncbi.nlm.nih.gov/pubmed/11834247

Serotonin increases: Research suggests that depletion of tryptophan, the amino acid precursor to serotonin (5-HT), does not cause hot flashes.  However, it has been noted that tryptophan depletion may increase susceptibility to hot flashes.  As was already mentioned, abnormally low serotonin upregulates the density of 5-HT receptors in the hypothalamus, which causes thermoregulatory dysfunction – causing a hot flash.

Effexor mitigates hot flashes specifically by increasing serotonin concentrations in the synaptic cleft, which leads to downregulation of hypothalamic 5-HT receptors to normalize thermoregulation.  That said, it is important to mention that serotonin levels may be directly related to stress, which in turn may be a direct underlying cause of hot flashes in certain individuals.  Literature indicates that high concentrations of epinephrine (adrenaline) and norepinephrine (noradrenaline) can provoke hot flashes.

These stimulatory neurotransmitters are typically released when our sympathetic nervous system is overactive and/or during the freeze-fight-flight response.  Due to the fact that Effexor increases concentrations of serotonin, users tend to feel less anxious and more relaxed.  In fact, it is well-documented that Effexor treats anxiety disorders – likely via its serotonergic effects.

Reductions in anxiety are known to decrease activation of the sympathetic nervous system, which in turn may minimize likelihood of hot flashes.  Furthermore, serotonin increases may also indirectly modify concentrations of certain hormones, as well as vasodilation/vasoconstriction processes that may cause hot flashes.  The bottom line is, since Effexor can reduce anxiety, and anxiety can cause hot flashes – a simple reduction of anxiety (from Effexor) may be one mechanism by which the occurrence of hot flashes decrease.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/9585103

Hormone concentrations: Individuals taking Effexor may experience alterations in concentrations of hormones.  Low levels of certain hormones (e.g. estrogen) are thought to cause hot flashes, hence the reason hormone therapy is considered a first-line intervention for women.  However, it is possible that to a small extent, Effexor has an impact on hormone levels and that this impact could predict likelihood of experiencing hot flashes.

A subset of patients develop conditions such as gynecomastia (slang: “man boobs”) as a result of Effexor-induced hormonal changes.  Laboratory assessments suggest that Effexor can increase serum levels of estradiol (E2) – a form of estrogen.  It can also affect circulating concentrations of hormones such as prolactin and luteinizing hormone.  Furthermore, there is some evidence that various antidepressants lower testosterone.

The myriad of hormonal changes induced by Effexor, particularly modest increases in estradiol (E2) may effectively attenuate hot flashes along with hypothalamic modulation and stress reduction via serotonergic alterations.  Perhaps a subset of women who respond favorably to Effexor as an intervention for hot flashes exhibit increased estrogenic activity (resulting from the medication).

• Source: http://www.ncbi.nlm.nih.gov/pubmed/18978497

Norepinephrine increases: There is some evidence to suggest that certain individuals derive minimal or insufficient therapeutic benefit from Effexor at low doses (37.5 mg to 75 mg/day) for the treatment of hot flashes.  At dosages of 150 mg to 300 mg per day, the drug is known to elicit greater norepinephrine reuptake inhibition, thereby increasing concentrations of norepinephrine within the synaptic cleft.

Certain theories discussing the biochemical causes of hot flashes suggest that central nervous system adrenergic neurotransmission can affect thermoregulatory processes.  Although it is understood that increasing serotonin can reduce hot flashes, it may be that simultaneous dual reuptake inhibition of both serotonin and norepinephrine could minimize likelihood of hot flashes – perhaps superior to standalone serotonergic reuptake inhibition.  Therefore, it is logical to suspect that among individuals who derive substantial benefit from moderate/high dose Effexor (for hot flashes), modulation of noradrenergic pathways contributes to hot flash reduction.

Effexor for Hot Flashes: A Non-Hormonal Therapy (Review of Research)

Whenever considering a particular treatment for hot flashes, it is necessary to investigate its efficacy as documented in scientific literature.  Upon assessment of the literature, there is a substantial amount of published research to support the efficacy of Effexor as an intervention for hot flashes.  In nearly every study, Effexor was found to be an effective non-hormonal treatment for hot flashes compared to a placebo.

2015: Venlafaxine in management of hot flashes in women with breast cancer: a systematic review and meta-analysis.

A systematic review and meta-analysis conducted by Ramaswami et al. (2015) assessed the efficacy of Effexor as a management strategy for hot flashes in women with breast cancer.  Systematic reviews are considered the highest quality form of scientific evidence, and for this reason, these reports often have real-world clinical implications.  To conduct this review of evidence, researchers compiled data (from randomized controlled trials) published until May 2015 involving venlafaxine (Effexor) as a treatment for hot flashes among women with breast cancer.

They assessed the efficacy of Effexor as an intervention by analyzing hot flash scores (as reported by patients).  These hot flash scores measured the severity and frequency of hot flashes among Effexor users.  Researchers then pooled results from the randomized controlled trials that met inclusion criteria and noted that Effexor significantly reduces hot flashes compared to other interventions.

It was concluded that pharmacological administration of Effexor effectively manages hot flashes among women with breast cancer.  Researchers noted that across all studies, there was significant heterogeneity and small study effects.  While additional research may strengthen existing findings, Effexor appears to be a viable intervention for hot flashes among women with breast cancer.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/26067931

2014: Sexual function in women on estradiol or venlafaxine for hot flushes: a randomized controlled trial.

A study published by Reed et al. (2014) sought to elucidate the sexual function of women taking low-dose estradiol (0.5 mg/day) or Effexor (75 mg/day) for hot flashes – as compared to a placebo.  Researchers set-up a randomized controlled trial among middle-aged women (40 to 62 years old) over the course of 8-weeks.  Sexual function was documented and compared using measures from the Female Sexual Function Index (FSFI) and sexually-related personal distress.

This study indicates that middle-aged women taking estradiol or Effexor for hot flashes didn’t experience changes in sexual function over a period of 8-weeks – compared to a placebo.  Results suggest that Effexor is unlikely to cause sexual dysfunction when administered as a non-hormonal intervention for hot flashes.  This evidence may be promising to women concerned that Effexor will decrease libido and/or ability to orgasm.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/25004335

2011: Venlafaxine and desvenlafaxine in the management of menopausal hot flashes.

A study conducted by Johnson and Carroll (2011) reviewed the efficacy and tolerability of Effexor, as well as its pharmacological successor Pristiq for the management of menopausal hot flashes.  Researchers noted that vasomotor flushes are commonly experienced by ~75% of women during (and after) menopause.  Although estrogen therapy is considered a first-line intervention for hot flashes, there are risks associated with this intervention (e.g. increased risk of breast cancer).

An alternative intervention is non-hormonal treatment with antidepressants such as Effexor and Pristiq.  The review of literature by Johnson and Carroll for studies published until June 2011 revealed that Effexor reduces hot flashes by 37% to 61%, whereas Pristiq reduces hot flashes by 55% to 69%.  Both SNRIs were well-tolerated with few adverse effects (e.g. dizziness, dry mouth, headache, nausea, etc.).

Researchers concluded that both Effexor and Pristiq are favorable non-hormonal treatments for reducing the occurrence and severity of hot flashes.  Women that are concerned about the risks associated with estrogenic interventions for hot flashes may want to consider Effexor and/or Pristiq.

• Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870169/

2010: Multicenter, randomized, cross-over clinical trial of venlafaxine versus gabapentin for the management of hot flashes in breast cancer survivors.

It is understood that both Effexor (Venlafaxine) and Neurontin (Gabapentin) are considered efficacious pharmacological interventions for hot flashes.  In 2010, a trial conducted by Bordeleau et al. compared Venlafaxine and Gabapentin head-to-head as treatments for hot flashes.  Researchers sought to determine whether there were differences in efficacy and/or tolerability.

For the trial, researchers set-up a group-sequential, open-label, randomized, crossover design for a period of 4-weeks.  Participants included 66 postmenopausal breast cancer survivors that experienced at least 14 troubling hot flashes per week for a month straight.  Researchers assigned the women to receive venlafaxine (37.5 mg/day for 7 days and 75 mg/day for 21 days) for 4-weeks or gabapentin (300 mg/day for 3 days and 300 mg/b.i.d. for 3 days, and 300 mg/t.i.d. for 22 days).

At baseline, all participants went 2 weeks without any treatment.  As part of the crossover design, there was a 2-week “washout phase” before the second (opposite) treatment was introduced.  Hot flashes were measured based on participant diaries and after the trial, outcomes were compared between Effexor and Neurontin.

A total of 56 participants completed the treatment, with 18 (32%) preferring gabapentin and 38 (68%) preferring venlafaxine.  Each intervention reduced hot flashes by around 66% – demonstrating similar efficacy.  Side effects slightly differed between the two treatments, but both were considered tolerable.

Effexor users experienced: mood improvement, nausea, constipation, and appetite reduction.  Gabapentin users experienced: dizziness and increased appetite.  Based on the results of this trial, researchers concluded that breast cancer survivors prefer Effexor over Neurontin for the management of hot flashes.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/21060031

2010: Acupuncture versus venlafaxine for the management of vasomotor symptoms in patients with hormone receptor-positive breast cancer: a randomized controlled trial.

A study by Walker et al. (2010) compared the efficacy of acupuncture and Effexor in the management of vasomotor symptoms associated with breast cancer.  Authors of the study mentioned that vasomotor symptoms such as hot flashes are commonly associated with antiestrogenic agents administered for the treatment of breast cancer.  Researchers conducted a randomized controlled trial (RCT) to determine whether Effexor decreases vasomotor symptoms compared to acupuncture – among those with breast cancer.

A total of 50 participants were divided into 2 groups of 25 and assigned at random to receive either: 12 weeks of Effexor or 12 weeks of acupuncture.  Researchers measured the health of participants for 1 full year after treatment.  Results indicated that both Effexor and acupuncture significantly decreased vasomotor symptoms such as hot flashes – during treatment.

However, upon discontinuation of treatments, the group receiving Effexor experienced notable increases in hot flashes.  The group receiving the acupuncture experienced no significant increases in hot flashes upon cessation of treatment.  Additionally, there were significantly more adverse effects reported among those taking Effexor, whereas none were reported among those receiving acupuncture.

Furthermore, acupuncture provided the benefit of increasing sex drive in a subset of women.  Researchers suggest that acupuncture appears as efficacious as pharmacological interventions such as Effexor for the treatment of vasomotor symptoms (e.g. hot flashes) associated with breast cancer.  Although acupuncture may be better tolerated and favorable over pharmacological treatments for hot flashes among women with breast cancer, Effexor should still be regarded as an effective intervention.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/20038728

2009: Use of antidepressants for management of hot flashes.

A study published by Carroll and Kelley (2009) analyzed the usage of antidepressants as an intervention for hot flashes.  Authors noted that there is significant evidence to suggest that SSRIs and Effexor (Venlafaxine) can manage symptoms of hot flashes.  The researchers scoured the literature of published studies (up to May 2009) documenting the efficacy of antidepressants for the treatment of hot flashes among women.

It was discovered that evidence to support usage of antidepressants for the treatment of hot flashes is conflicting.  They noted that the antidepressants Effexor and Paxil have been the most researched and appear to be effective for the treatment of hot flashes, whereas other antidepressants may be less effective.  Authors concluded that when treating hot flashes with antidepressants, Effexor and Paxil should be considered first-line options; other antidepressants should be reserved for usage as second-line, third-line, and last-resort options.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/19857151

2007: Randomized, double-blind, placebo-controlled crossover trials of venlafaxine for hot flashes after breast cancer.

Two trials conducted by Carpenter et al. (2007) documented the efficacy of Effexor for the treatment of hot flashes among breast cancer survivors.  These trials were randomized, double-blinded, placebo-controlled, and crossover.  Researchers primarily measured occurrence of hot flashes among those receiving Effexor, and recorded secondary measures of mood, energy, sleep, and quality of life.

A total of 57 breast cancer survivors were recruited from cancer clinics to participate in a low-dose study, while 20 were recruited for a higher-dose study.  In the low-dose study, participants were administered 37.5 mg venlafaxine, whereas in the higher-dose study, participants were administered 75 mg venlafaxine.  Throughout the study, frequency and severity of hot flashes were recorded with diaries, event markers, and physiological monitors.

Results indicated that administration of venlafaxine modestly decreased hot flashes.  A greater reduction in hot flashes was noted among those taking the higher (75 mg) dose.  Researchers noted that despite Effexor’s efficacy for the treatment of hot flashes, most patients opted to discontinue treatment over a long-term.  This suggests that although Effexor is clinically effective in reducing hot flashes, it may not be a viable long-term treatment.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/17227907

2007: Alleviation of Hot Flashes With Increase in Venlafaxine Dose.

Medical doctors Padala et al. (2007) highlighted a case in which hot flashes were alleviated with an upward titration in Effexor dosage.  The case involved a 54-year-old woman who was being treated with Abilify for schizoaffective disorder and Effexor (75 mg) for depression.  A review of her medical history indicated no reports of alcohol and/or drug usage within 20 years.

In addition to taking Abilify and Effexor, the woman was prescribed Lamictal (200 mg/b.i.d.), metoprolol (12.5 mg/b.i.d.), rosiglitazone 4 mg/daily, simvastatin 40 mg/nightly, phenytoin 300 mg/nightly, and temazepam 15 mg/p.r.n.  In the case of this woman (referred to as “Mrs. A”) she complained of nearly 8 to 10 hot flashes per day for the previous 3 months.  Each of her hot flashes reportedly lasted for 20+ minutes with flushing and feelings of cold.

Doctors increased her dosage of Effexor from 75 mg to 150 mg per day based on the evidence that Effexor can decrease hot flashes.  Following the dosage increase of Effexor, Mrs. A was noted as exhibiting reductions in frequency and severity of hot flashes.  Number of hot flashes decreased to 2 per day (rather than 8 to 10) and duration of hot flashes decreased from 20+ minutes to between 5 and 10 minutes.

Although hot flash severity and frequency had decreased following the upward titration in Effexor dosing, the woman reported tremors as a side effect.  Doctors attributed tremors to increased concentrations of norepinephrine (as occur at higher doses of Effexor).  Sensibly, the doctors decreased her dosage of Effexor back to 75 mg and noted that the tremors decreased.

However, hot flash severity and frequency increased once again as a result of a drop in the dosage.  Once again, researchers increased her Effexor dosage from 75 mg/day back to 150 mg/day and sought the help of a neurologist for the tremors.  Researchers speculate that the combination of serotonergic and noradrenergic changes induced by the 150 mg dose may be superior for altering thermoregulation to decrease hot flashes (in certain users).

They document that Effexor is considered effective as a treatment for hot flashes in postmenopausal women and that its therapeutic efficacy may be contingent upon dosage administered.  As was highlighted in this case report, some users appear to derive more substantial benefit from dosage increases.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/17599176

2005: Evaluation of low-dose venlafaxine hydrochloride for the therapy of hot flushes in breast cancer survivors.

Researchers Biglia et al. (2005) evaluated the efficacy and tolerability of long-term, low-dose Effexor administration for the treatment of vasomotor symptoms among breast cancer survivors.  They set up a trial in which 40 breast cancer patients received Effexor XR (extended-release) at 37.5 mg/day for a period of 8-weeks.  Vasomotor symptoms (e.g. hot flashes) were evaluated prior to treatment, as well as every 4-weeks thereafter throughout the trial.

Additionally, mood of the participants was recorded with the BDI (Beck Depression Inventory).  Results indicated that among the 30 participants that completed the initial 4-weeks of treatment, hot flashes were reduced significantly in frequency (by 39%).  Following 8 consecutive weeks of treatment, additional reduction in hot flashes was reported – in both frequency and severity (over 50%).

Participants didn’t appear to experience many significant side effects, with dry mouth and nausea being the most common.  At the end of 8-weeks, a 23% decrease in depressive symptoms was reported based on BDI scores.  Based on results, researchers concluded that Effexor (37.5 mg/day) was an effective, well-tolerated treatment for vasomotor symptoms among breast cancer survivors.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/16143229

2005: Management of postmenopausal hot flushes with venlafaxine hydrochloride: a randomized, controlled trial.

A study conducted by Evans et al. (2005) documented the efficacy of Effexor XR as a treatment for postmenopausal hot flashes.  For the study, researchers recruited 80 postmenopausal women who reported experiencing at least 14 hot flashes per week.  Participants were divided evenly into 2 groups of 40 and assigned to receive either: Effexor XR (37.5 mg/day for 1 week and 75 mg/day for 11 weeks) or a placebo (once daily) – for a duration of 12 weeks.

To gauge the efficacy of Effexor XR as a treatment for hot flashes, researchers recorded daily hot flash severity among participants at pre-treatment baseline, as well as throughout the study.  In addition, secondary measures of quality of life and sexual function were collected.  A total of 61 participants completed the study (29 receiving Effexor and 32 receiving the placebo).

Results indicated that subjective hot flash symptoms significantly improved among those receiving Effexor XR compared to those taking the placebo.  However, daily severity of hot flashes as measured by diaries indicated no significant difference between those taking Effexor XR and the placebo.  Furthermore, the group receiving Effexor XR experienced side effects of: dry mouth, appetite loss, and insomnia.

Authors noted that 93% of individuals receiving Effexor XR opted to continue with treatment upon conclusion of the trial.  Based on the patient-perceived hot flash score ratings, Effexor XR was effective in treating postmenopausal hot flashes.  However, based on objective diary reports – there was no statistical difference, making it difficult to recommend Effexor as a treatment for hot flashes.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/15625158/

2003: Venlafaxine hydrochloride for the treatment of hot flashes.

In 2003, researchers Schober and Ansani published a report analyzing the existing literature of Effexor as a treatment for hot flashes.  They attained data from trials published between 1966 and August 2002 within PubMed, Harrison’s Online, and other references.  Upon reviewing the data, researchers discovered that not all individuals exhibiting hot flashes are ideal candidates to receive standard hormone therapy.

For this reason, non-hormonal interventions such as antidepressants (e.g. Effexor) may be suitable options.  After reviewing the totality of published research, authors concluded that Effexor is an effective non-hormonal treatment for uncontrollable hot flashes.  Those who are unfit for hormone therapy may derive benefit from Effexor.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/14565812

2002: Venlafaxine for the control of hot flashes: results of a longitudinal continuation study.

In 2002, Barton et al. published a study evaluating the efficacy and toxicity of Effexor for the control of hot flashes over a moderate-term.  Researchers devised an open-label, continuation phase study with a double-blind, randomized, placebo-controlled design.  The trial aimed to compare three dosages of Effexor among 102 postmenopausal women.

To assess hot flash severity and frequency, a composite “hot flash score” was recorded for each of the participants.  All women were allowed to adjust their Effexor dosage throughout the study to a quantity that provided most benefit.  Results indicated that there were no toxicity issues, and that Effexor appeared to be a well-tolerated, effective treatment for hot flashes over a moderate-term of administration.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/11817491

2000: Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial.

A trial conducted by Loprinzi et al. (2000) assessed the efficacy of Effexor for the management of hot flashes among breast cancer survivors.  Researchers noted that hot flashes can be particularly bothersome among individuals unable to pursue hormone therapy.  Hormone therapy is considered a first-line intervention for hot flashes, but is contraindicated among breast cancer survivors due to the fact that it may cause a recurrent bout of breast cancer.

Due to the fact that there is some evidence suggesting that antidepressants such as Effexor can reduce hot flashes, researchers set up a double-blind, placebo-controlled, randomized trial to further elucidate its therapeutic efficacy in reducing hot flashes.  A total of 221 individuals were recruited for the study and assigned either a placebo or varying dosages of Effexor.  Specifically, 56 took the placebo, 56 took 37.5 mg Effexor per day, 55 took 75 mg Effexor per day, and 54 took 150 mg Effexor per day.

Prior to the trial, all participants underwent baseline assessments to determine the severity of their hot flashes.  Following the baseline assessments, participants received either the placebo or Effexor for a duration of 4 weeks.  Throughout the study, hot-flash questionnaire diaries were completed by patients and average hot flash activity per day was compared to the pre-treatment baseline.

After 4-weeks, results were derived from 191 participants that provided adequate data for interpretation throughout the entire study period.  Of these 191 participants, 50 took the placebo, 49 took the 37.5 mg Effexor, 43 took the 75 mg Effexor, and 49 took the 150 mg Effexor.  Results indicated that hot flash scores were significantly reduced among individuals taking Effexor compared to the placebo.

Interpretation of these findings indicates that those taking the 75 mg and 150 mg doses experienced greater therapeutic benefit than those taking 37.5 mg or the placebo.  Therefore, it should be recommended that when administering Effexor as a non-hormonal treatment for hot flashes – dosages of at least 75 mg should be taken.  This study bolsters existing evidence suggesting the therapeutic efficacy of Effexor as a non-hormonal treatment for hot flashes.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/11145492/

1999: Pilot evaluation of venlafaxine for the treatment of hot flashes in men undergoing androgen ablation therapy for prostate cancer.

A study published in 1999 by Quella et al. noted that hot flashes may be a major problem among men undergoing androgen deprivation therapy (ADT), also called androgen suppression therapy – for prostate cancer.  Androgen deprivation therapy may involve gonadotropin releasing hormone analogues, oral antiandrogens, and/or other surgical procedures.  Due to the severity and number of hot flashes experienced by men during this therapy, researchers speculated that intervention with a non-hormonal agent such as Effexor may prove therapeutic.

As a result, they set up a trial involving men that experienced significant hot flashes during androgen deprivation therapy.  Prior to the trial, baseline measures were collected with daily questionnaires for a 1-week period – this determined a hot flash score (based on number of flashes and severity of flashes).  Thereafter, all participants received 12.5 mg Effexor twice per day (b.i.d.) for a total of 25 mg per day – for a duration of 4-weeks.

A total of 16 participants completed the study, and a total of 10 exhibited significant reduction in hot flash scores (by at least 50%), indicating that frequency and severity of hot flashes was reduced by Effexor treatment.  Occurrences of “severe” and “highly severe” hot flashes decreased from over 2 per day (at baseline) to an average of 0.6 per day by the end of the 4-week term.  Researchers concluded that therapy was well-tolerated and that Effexor appears to be an effective intervention for the treatment of hot flashes among men undergoing androgen deprivation therapy (ADT).

• Source: http://www.ncbi.nlm.nih.gov/pubmed/10379749

Verdict: Effexor is an effective non-hormonal treatment for hot flashes

In nearly every published research paper investigating Effexor (Venlafaxine) as a treatment for hot flashes, it was discovered to be effective in reducing both the frequency and severity of hot flashes.  This efficacy was most substantial among individuals receiving dosages of 75 mg to 150 mg per day.  Lower dosages such as 37.5 mg per day appeared to provide less benefit than moderate dosages, perhaps suggesting that the serotonergic and noradrenergic mechanisms of Effexor synergistically alleviate hot flashes.

Although most studies investigated the efficacy of Effexor among women, there is even some evidence to suggest that men experiencing hot flashes can also benefit from Effexor as a non-hormonal intervention.  Effexor may be an important non-hormonal intervention for the treatment of severe hot flashes, especially when considering the fact that not all individuals tolerate hormone replacement therapy as a first-line treatment.  For example, hormone replacement therapy is contraindicated among breast cancer survivors, leaving them with few other pharmaceutical options for the treatment of hot flashes.

There aren’t any major limitations associated with the research of Effexor for hot flashes – most studies are well-designed, randomized, placebo-controlled, and incorporate large sample sizes.  Furthermore, most research suggests that Effexor is well-tolerated by most individuals, yielding few unwanted side effects.  Since Effexor also exhibits propensity to improve mood (via antidepressant effects), as well as reduce anxiety, it may be an especially favorable option for individuals with major depression and comorbid hot flashes.

Benefits of using Effexor for hot flashes (Possibilities)

If contemplating whether to pursue Effexor as a treatment for hot flashes, it may be helpful to consider the hypothetical benefits that it may provide.  In addition to effectively reducing severity and frequency of hot flashes, Effexor may also reduce your anxiety/stress and improve your mood.  Furthermore, you won’t need to worry about the increased risk of breast cancer associated with hormone therapy (as Effexor is non-hormonal).

• Anxiety/stress reduction: There is robust evidence to suggest that Effexor reduces many forms of anxiety. If you have an anxiety disorder (e.g. generalized anxiety disorder), you should know that Effexor has been approved by the FDA as a treatment for this condition.  Individuals with anxiety disorders or high stress and concurrent hot flashes may treat both conditions with a single pill.
• Effective: The efficacy of Effexor as a treatment for hot flashes is well-established. The literature investigating its efficacy for the management of hot flashes dates back to the late 1990s.  Nearly all research that has tested Effexor specifically for the management of hot flashes has documented its clinical efficacy.  Although Effexor may not reduce hot flashes for everyone, the scientific evidence suggests that it has a good chance of working.
• Mood improvement: Many individuals experiencing hot flashes also struggle with depression and/or low mood. Effexor was first approved by the FDA in 1993 for the treatment of depression, and the drug was specifically engineered to attenuate depressive symptoms.  If you have major depression and comorbid hot flashes – this drug may help control both conditions.
• Non-hormonal: A major advantage associated with Effexor over other treatments is that it’s non-hormonal. Many women, particularly breast cancer survivors and/or those afraid to use hormone replacement therapy (due to its link to cancer) may want an alternative pharmaceutical treatment for hot flashes.  Effexor doesn’t radically alter hormones (although it may increase “E2” estradiol slightly in some individuals) and therefore may be less likely to cause breast cancer.  Furthermore, since hormone replacement therapy is intolerable and/or contraindicated among some individuals experiencing hot flashes, Effexor is considered a favorable non-hormonal (potentially less risky) alternative.
• Well-being: Effexor’s mechanism of action involves increasing extracellular concentrations of serotonin, and to a lesser extent, norepinephrine. Increasing concentrations of these neurotransmitters in the synaptic cleft is thought to improve communication between neurons, thereby improving someone’s mood.  Although this effect may be most noticeable among individuals with major depression, Effexor may make some non-depressed persons feel “better than well” or as if their well-being has improved.
• Well-tolerated: Though Effexor may cause a few unwanted side effects, most users tolerate the drug well. Effexor isn’t likely to cause significant weight gain or fatigue compared to other antidepressants.  In a head-to-head study comparing Effexor to another popular drug (Gabapentin) for the treatment of hot flashes, it was noted that most users preferred Effexor.  Some trials suggest negligible differences in tolerability between Effexor and a placebo – indicating that it is well-tolerated.

Drawbacks of using Effexor for hot flashes (Possibilities)

Effexor should not be viewed as some utopian, non-hormonal treatment for hot flashes or any condition – there are drawbacks associated with using Effexor.  The drug is associated with unwanted side effects such as dry mouth, appetite changes, and (ironically) hot flashes.  Additionally, Effexor’s efficacy is usually unsustainable over a long-term and long-term usage may scramble your neurochemistry to such an extent, that upon discontinuation, you experience deleterious, protracted withdrawal symptoms.

• Causes hot flashes: Although Effexor usually decreases hot flash scores (frequency and severity), some users report an increase in hot flashes after treatment. This may be due to the fact that Effexor increases concentrations of norepinephrine.  Heightened levels of norepinephrine can increase core body temperature and modify thermoregulatory processes, thereby triggering hot flashes in certain users.  While not everyone will experience hot flashes while taking Effexor, this may be viewed as an ironic side effect among those attempting to reduce the occurrence of hot flashes.
• Chemical imbalance: Many people (even professionals) fail to realize that there’s no such thing as a biological free lunch. The alterations in neurotransmission (as induced by Effexor) aren’t able to bypass the built-in homeostatic hardwiring of the CNS.  For this reason, as a person continues to use Effexor, the user’s neurophysiology compensates via changes in connectivity, receptor densities, neural activation, etc.  Eventually the drug stops working and when removed (or discontinued), the user is left with an antidepressant-induced chemical imbalance (that often takes awhile to correct).
• Daily usage required: Effexor is not something that can be taken on an “as needed” basis for the treatment of hot flashes. When taking Effexor, it is necessary to take it every single day.  Due to the fact that Effexor is required to be taken daily, the user’s neurophysiology is constantly under the influence of an exogenous substance.  Some people may dislike the fact that they are under the influence of a medication 24 hours per day, 7 days a week, etc. – simply to manage hot flashes.  Forgetting to take a daily dose may result in flu-like symptoms and dreaded cortical shocking sensations known as “brain zaps.”
• Favorable alternatives: Certainly it is understandable to consider Effexor as an alternative to hormone replacement therapy for the treatment of hot flashes. However, there appear to be many non-pharmacological interventions for the management of hot flashes such as acupuncture and simple lifestyle changes.  One study noted that acupuncture is equally as effective as Effexor for hot flashes.  Many people fail to investigate alternatives that may be safer, less risky (especially over the long-term), and equally as effective as Effexor in reducing hot flashes.
• Long-term effects: Even though Effexor has been on the market since 1993, the long-term effects aren’t fully understood. Although individuals taking the drug for hot flashes may only require temporary treatment with Effexor, some may require sustained, long-term treatment.  It is possible that users may experience deleterious long-term health complications and/or risks as a result of Effexor.  Studies suggest the safety of Effexor when used for long periods, but not over periods exceeding several years.
• Side effects: The literature indicates that Effexor is generally well-tolerated by users. However, not everyone can take Effexor without some side effects and/or adverse reactions.  Some individuals may report that Effexor causes weight changes, dry mouth, dizziness, headaches, nausea, and insomnia.  There are “black box” warnings suggesting that Effexor may increase suicidal thoughts and/or depression in certain users.  That said, to know whether you’re likely to experience unwanted side effects – you may want to get GeneSight testing.  Effexor is metabolized by CYP2D6 isoenzymes and if you have a specific polymorphism – you may be more prone to side effects.
• Unsustainable efficacy: Many people wonder why antidepressants stop working when taken over an extended duration; this happens with many other forms of medications as well. The body adapts to the drug, and even when the dosage is increased, body adapts to the increase, and the cycle perpetuates until the drug is no longer tolerable and/or effective.  It is unlikely that Effexor will work “forever” for the treatment of hot flashes.  Though its efficacy over short and moderate terms is established, efficacy over a period of years or decades is unlikely maintained.
• Withdrawal symptoms: Perhaps the biggest reason to think twice about using Effexor for the treatment of hot flashes is that when discontinued, you’ll experience hellacious Effexor withdrawal symptoms. There are countless testimonials from former Effexor users suggesting that if they had known the severity of discontinuation prior to taking the drug, they’d have never taken Effexor in the first place.  Although Effexor may be helping your hot flashes, not only will hot flashes reemerge upon Effexor cessation, but a host of other (new) symptoms will as well.

Why Effexor should be considered a last-resort for hot flashes…

There is robust evidence to support the usage of Effexor for hot flashes, but that doesn’t mean it’s necessarily a safe intervention or targeting the root of the problem.  Just because a pharmaceutical drug effectively treats a condition, does not mean that it should automatically be utilized.  Just like you could use an atomic bomb to clear a weed growing in your garden – doesn’t mean you should.

Perhaps the atomic bomb analogy is a bit extreme.  However, the point to be made is that just because something works or effectively treats a condition (e.g. hot flashes) – doesn’t mean you should automatically pursue it.  Although the literature suggests Effexor reduces the occurrence of hot flashes as a non-hormonal intervention, the risks associated with using an SNRI antidepressant for the management of hot flashes are significant – and undermined by mainstream media.

Many people start taking Effexor for hot flashes based on a recommendation from their doctor – without giving any thought to what the drug is actually doing.  Most users don’t fully comprehend the potentially deleterious neurophysiological consequences associated with using a potent antidepressant such as Effexor for hot flashes.  Using Effexor is altering your neurophysiology to a significant extent – on a daily basis.

With continued usage, your brain circuitry and physiology adjusts to expect the drug in circulation.  Eventually you’re going to reach a point where you may feel as if you cannot function without Effexor.  You may try to discontinue treatment only to feel angry, anxious, depressed, irritable, moody, etc. – and experience a resurgence in your hot flashes.

Unless you are experiencing refractory hot flashes for which no safer and/or first-line treatment is available, Effexor shouldn’t be utilized.  Even the FDA advisory boards have voted against the usage of antidepressants and/or off-label, non-hormonal interventions for the treatment of hot flashes.  Effexor isn’t some modest pharmaceutical with minimal effects, it is a potent antidepressant that should be reserved for individuals with serious neuropsychiatric conditions such as major depressive disorder (MDD).

Scenarios when Effexor may be practical for hot flashes…

There are really only a couple scenarios when it makes logical sense to use Effexor as a treatment for hot flashes.  The first case would be among individuals diagnosed with major depression and/or an anxiety disorder who is experiencing hot flashes.  The second case would be among individuals who have pursued all medically recommended first-line treatments for hot flashes, as well as alternative interventions without any relief.

1. Depression/Anxiety with Hot Flashes

If you have been diagnosed with major depressive disorder (MDD) and/or an anxiety disorder, and simultaneously experience debilitating hot flashes – utilization of Effexor may be optimal.  Effexor is known to provide robust antidepressant and anxiolytic efficacy, as well as treat hot flashes.  Assuming you have either a depressive or anxious disorder, you’d be able to target the debilitating neuropsychiatric condition via modulation of monoamines, and reap the added benefit of reducing hot flashes.

2. Refractory Hot Flashes

Individuals that have pursued first-line treatments for hot flashes and alternative non-pharmacological treatments (e.g. lifestyle changes, stress reduction, acupuncture) may not respond.  If you have refractory or unresponsive hot flashes, and they are perceived as highly debilitating (interfering with your daily functioning) – you may opt to test Effexor.  Though Effexor shouldn’t be used as a first-line treatment, functional impairment resulting from treatment-resistant hot flashes may be necessary to treat with Effexor.

Have you used Effexor for hot flashes?

If you’ve used Effexor as a treatment for hot flashes, share your experience in the comments section below.  Mention whether you have an underlying neuropsychiatric condition along with hot flashes, or solely hot flashes that were being treated with Effexor.  Document how Effective you perceived the Effexor to be as a treatment for hot flashes, as well as any additional favorable benefits you noticed while taking it (e.g. a mood improvement).

Also share any unwanted side effects (or drawbacks) you experienced as a result of Effexor.  To help others get a better understanding of your situation, share the dosage of Effexor that you’re taking – as well as whether you’re taking other medications and/or supplements.  Have you tried any other treatments for hot flashes such as hormone replacement therapy (HRT) or alternative interventions such as acupuncture?

Realize that there is ample evidence to support the usage of Effexor for the treatment of hot flashes.  However, if hot flashes are the only condition you’re treating with Effexor, you may want to reconsider treatment and the consequences associated with using a potent antidepressant as a non-hormonal intervention (e.g. neurochemistry changes, side effects, withdrawal symptoms, etc.).  Do you think Effexor should be used as a treatment for hot flashes? Why or why not?

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