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Effexor (Venlafaxine) For Anxiety Disorders: An Effective Anxiolytic?

Effexor (Venlafaxine) is a drug that was introduced in 1993 as a pharmaceutical antidepressant by Wyeth; its marketing rights are now owned by Pfizer.  Pharmacodynamically, it functions primarily as a serotonin-norepinephrine reuptake inhibitor (SNRI) and is understood to be the first-ever “dual reuptake inhibitor” approved by the FDA for the treatment of major depressive disorder.  Unlike selective-serotonin reuptake inhibitors (SSRIs) which solely modify serotonin levels, Effexor simultaneously increases extracellular levels of both serotonin and norepinephrine.

Following its initial approval for the treatment of major depression, it was subject to additional clinical trials as an anxiolytic.  Thereafter, it was discovered to be efficacious and attained FDA approval for the treatment of generalized anxiety disorder (GAD), panic disorder, and social phobia.  Although it is understood that increasing extracellular norepinephrine can worsen symptoms of anxiety, Effexor predominantly affects serotonin (to nearly 30-fold the extent) – facilitating an anxiolytic effect.

Despite the fact that Effexor is an older medication from the 1990s, it is still regarded as a clinically effective pharmacological intervention for the treatment of anxiety disorders.  Many individuals prefer Effexor over other antidepressants for anxiety because it has a favorable side effect profile (e.g. minimal weight gain), and can mitigate comorbid depressive symptoms.  Moreover, it is a well-researched drug and often “kicks-in” (starts working) quicker than other antidepressant anxiolytics.

How Effexor May Treat Anxiety Disorders (Mechanisms)

When considering Effexor as an anxiolytic, it may be beneficial to understand how it treats anxiety disorders.  Being classified as an SNRI, we can speculate that anxiety reductions stem primarily from its affinity to increase extracellular serotonin.  However, among those that derive anxiolytic benefit from high doses, partial anxiolytic benefit may be generated via increases in extracellular norepinephrine, and in some cases, dopamine.

Increases serotonin: Research suggests that individuals with anxiety disorders often exhibit suboptimal signaling and/or extracellular concentrations of monoamines, particularly serotonin.  Trials of drugs such as SSRIs and SNRIs (such as Effexor) indicate that targeting the neurotransmission of serotonin via reuptake inhibition, significantly reduce various types of anxiety.  Although serotonin shouldn’t be regarded as the direct or sole cause of anxiety disorders, it is understood that increasing extracellular serotonin attenuates anxious symptoms.

Since Effexor modifies serotonergic transmission to nearly 30-times the extent of norepinephrine, it should be suspected that most of the anxiolytic benefit is attained via alterations of the serotonin system.  Other SNRIs such as Cymbalta, Pristiq, and Fetzima are not typically effective for the treatment of anxiety disorders because they exhibit less significant targeting of serotonin relative to norepinephrine.  As a result, these other agents are considered effective for depression, but may exacerbate some cases of anxiety.

Increases norepinephrine: It is necessary to consider that some individuals with atypical anxiety disorders may benefit from the increases in extracellular norepinephrine as generated by Effexor.  Perhaps the slight increases in norepinephrine (relative to serotonin) provide additional stimulation to improve cognitive processes, energy, and/or motivation – each of which may decrease anxiety.  A subset of individuals with anxiety disorders may complain of “brain fog” and/or relaxation-induced anxiety (from excessive relaxation).

The reuptake inhibition of norepinephrine may increase a user’s neurophysiological arousal just enough to decreased anxiety associated with feeling “spaced out” or overly relaxed.  Since the norepinephrine increases generated by Effexor aren’t significant when compared to serotonin, users are unlikely to feel overly-energetic or jittery.  Although noradrenergic properties are unlikely to significantly contribute to anxiolytic effects of Effexor when compared to serotonergic properties, the combination of both may be helpful for certain cases of anxiety.

Dopamine increases: Most individuals using Effexor for anxiety are unlikely to be administering high doses.  At high doses, the pharmacodynamics of the chemical venlafaxine are altered.  Although reuptake inhibition of serotonin and norepinephrine remain in tact, high-dose venlafaxine can elicit modest (or negligible) dopamine reuptake inhibition (DRI), thereby increasing dopamine concentrations in the extracellular space.

What’s more is that Effexor’s propensity to inhibit the norepinephrine transporter (NET) at high doses indirectly increases dopaminergic transmission in the prefrontal cortex.  It is known that some individuals may experience anxiety as a result of poor dopamine signaling and/or low dopamine.  For this reason, it is necessary to speculate that increasing dopamine to a modest extent (among high-dose users), could (subtly) contribute to an anxiolytic effect.

Opioidergic effects: Newer evidence suggests that venlafaxine is an indirect opioid receptor modulator.  In animal research, venlafaxine administration appeared to exhibit a dose-dependent analgesic effect, resulting in attenuation of pain responses.  It is unclear as to what extent opioidergic neurotransmission is affected among humans taking Effexor, but it may contribute to an anxiolytic effect.

  • Mu opioid receptor (MOR)
  • Kappa opioid receptors (KORs)
  • Delta opioid receptor (DOR)

Many individuals derive significant anxiolytic benefit from administration of potent opioids such as morphine, oxycodone, and hydrocodone.  Unfortunately, the anxiolytic effects of these agents are unsustainable with long-term, regular administration.  Though the opioidergic effects of Effexor are likely minimal and only attained at high-doses, they should be considered to yield anxiolytic benefit.

Benefits of Effexor for Anxiety (Possibilities)

There are some obvious advantages associated with using Effexor as a treatment for anxiety disorders.  Unlike various dietary supplements and off-label anxiolytics, Effexor has undergone rigorous clinical testing and received FDA approval to treat several types of anxiety.  Furthermore, it is relatively fast acting compared to similar drugs, is well-researched (having been around since the early 1990s), and isn’t associated with severe unwanted side effects.

  • Alternative to SSRIs: Some individuals fail to derive anxiolytic benefit from SSRIs due to the fact that they solely modulate serotonergic transmission. Although Effexor affects serotonin to a significant extent, it also alters concentrations of norepinephrine – which may decrease anxiety in a subset of individuals.  It is also necessary to consider that Effexor may modestly alter levels of dopamine and mediate opioid receptors when prescribed at high doses – each of which could reduce anxiety.
  • Cognitive function: Studies have shown that Effexor is capable of reversing cognitive impairment. Since cognitive impairment and/or deficits can increase a person’s anxiety, it may be necessary to consider that for certain individuals, anxiety may decrease as a result of cognitive enhancement.  Research shows that venlafaxine increases BDNF levels in the CA3 area within the hippocampus of rats, likely stimulating neurogenesis (the growth of new neurons); this may be the mechanism by which cognitive deficits are attenuated.
  • Clinically effective: Effexor is not only considered safe by FDA standards, but it is regarded as clinically effective. In other words, it was extensively evaluated as a treatment for anxiety, and was found to be significantly more effective than a placebo in randomized, double-blinded trials.  Research shows that Effexor is an effective treatment for various types of anxiety including: generalized anxiety disorder (GAD), panic disorder, and social phobia.  Additionally, Effexor is considered effective regardless of a user’s age; studies document its efficacy among children, adults, and elderly patients.
  • Dose-dependent effects: The effects elicited by Effexor upon neurotransmission can be modified based on the dosage administered. When administered at a low dose, serotonin reuptake inhibition is the primary effect.  However, when administered at high doses, other neurotransmitters such as norepinephrine (and to a smaller extent, dopamine) are increased in the extracellular space.  Additionally, subtle nociceptive effects have been noted via indirect opioidergic modulation at high doses.  Dose-dependent effects may be advantageous in that a low dose may not provide anxiolytic benefit for a particular user, but a high dose could; and vice-versa.
  • Fast-acting: Many antidepressants take a long time to work or elicit a therapeutic effect. A majority of SSRIs take between 4 to 8 weeks for users to report benefits.  Although Effexor may take several weeks to “kick in” as well, many users find that it works much quicker.  In fact, some users have reported experiencing significant therapeutic relief from Effexor within the first week of administration; this fast-action may be notably advantageous for severe cases of anxiety.
  • Minimal interactions: Compared to many older compounds, Effexor is considered to have minimal interactions with other psychiatric drugs. This means that a psychiatrist is capable of prescribing adjunct (or “add-on”) anxiolytics along with it.  If you take Effexor, a psychiatrist may recommend an adjunct such as Buspar, a benzodiazepine, or even a beta blocker to bolster anxiolytic relief derived from venlafaxine.
  • Monoaminergic modulation: Those with abnormal concentrations of monoamines, particularly serotonin, may benefit from administration of Effexor. When administered at high doses, Effexor can act as an SNDRI or “triple reuptake inhibitor.”  Though it doesn’t affect dopamine to a significant extent, its ability to modulate serotonin and norepinephrine may simultaneously treat both anxious and depressive symptoms.
  • Mood improvement: Those that are struggling with anxiety and comorbid depression (or vice-versa) could essentially treat two conditions with one pill. Effexor was originally approved for the treatment of major depressive disorder and is understood to be a highly-effective antidepressant.  If you have anxiety along with depression, this drug may be helpful for the management of both psychiatric conditions.
  • Neurophysiologic stimulation: Many cases of anxiety are caused by overstimulation, leading to a “freeze-fight-flight” response. However, some individuals with anxiety may feel anxious as a result of suboptimal stimulation.  In other words, their sympathetic nervous system and/or brain may not be generating enough stimulatory neurotransmitters to keep them cognitively engaged and/or focused with the external world.  This lack of cognitive stimulation can lead a person to feel spaced out, fatigued, and anxious as a result.  Bolstering neurophysiologic stimulation and arousal via norepinephrine increases may contribute to Effexor’s anxiolytic effect.
  • Side effect profile: Compared to many serotonergic antidepressants prescribed for anxiety, Effexor may have a favorable side effect profile. Effexor isn’t associated with significant weight gain, fatigue, and/or sexual dysfunction that is often reported among SSRI users.  In fact, some people may end up losing weight and/or exhibit increased libido from Effexor’s noradrenergic stimulation.
  • Well-researched: Although many people are excited about new medications for anxiety (2015) in development, as well as recently approved anxiolytics, the long-term safety of these novel “new” anxiolytics will remain unknown until they’ve been around for awhile and subject to additional research. Effexor has been on the market for over 20 years and has undergone extensive testing.  It has proven itself as an effective drug with minimal risks of deleterious long-term effects.

Drawbacks of Effexor for Anxiety (Possibilities)

Although there are numerous benefits associated with using Effexor as a treatment for anxiety, it is clearly not a utopian anxiolytic for all users.  Various drawbacks associated with Effexor usage include: long-term effects, unwanted side effects, unsustainable efficacy, and/or a possible worsening of anxiety.  Though the benefits may significantly outweigh the drawbacks for many users, others will derive no anxiolytic benefit from Effexor.

  • Excess stimulation: At high doses in particular, Effexor may be too stimulating for a subset of users. Although it isn’t considered as stimulating as other SNRIs, its propensity to increase extracellular concentrations of norepinephrine can lead to activation of the sympathetic nervous system.  This sympathetic activation may result in users feeling excessively anxious, restless, and/or jittery.
  • Ineffective: There’s no guarantee that Effexor will provide every user with clinically significant anxiety relief. For certain users, Effexor may be completely ineffective for the treatment of anxiety.  Just because it is FDA approved as an anxiolytic and functions by increasing extracellular levels of monoamines (e.g. serotonin), does not make it universally effective.  If you’re using Effexor for anxiety, there’s a chance that you may experience no anxiolytic effect from its usage.
  • Long-term effects: The effects of long-term Effexor administration aren’t fully understood. Although the drug is considered a safe anxiolytic and antidepressant for a long-term, extended durations of usage (e.g. several years) may yield deleterious effects.  Over time, your neurophysiology will adapt to regular Effexor administration, and if you’ve increased your dosage, unwanted effects may emerge with long-term treatment.
  • Side effects: Though the side effect profile of Effexor is considered favorable over other antidepressants, it is not perfect. Examples of common Effexor side effects include: blurred vision, drowsiness dry mouth, and nausea.  Additionally, some users may report Effexor causes weight gain or sexual dysfunction.  Side effects are most common among CYP2D6 poor metabolizers, but may lead a user to discontinue treatment if severe.
  • Slow acting: In some cases, Effexor works right away (within the first few days of administration), but in other cases, it may take weeks to fully “kick-in.” If you have severe anxiety and need immediate symptomatic relief, there may be faster-acting pharmacological interventions.  Many FDA-approved anxiolytics elicit nearly instantaneous anxiolytic effects such as benzodiazepines.
  • Superior options: Due to the fact that Effexor increases concentrations of norepinephrine, it may be inferior to SSRIs for the treatment of anxiety disorders. Furthermore, there are many other ways to deal with anxiety that may be faster-acting with fewer side effects (e.g. Buspar).  For this reason, those considering Effexor for anxiety may want to review other possible anxiolytic interventions.
  • Unsustainable efficacy: For many individuals, Effexor can decrease anxiety for a period of months or even several years. However, when administered regularly over an extended term, its efficacy is not usually sustainable.  A user will likely develop tolerance to its effects, leading the user to perceive that it is no longer effective.  Though you may be able to reap the anxiolytic benefits of Effexor for a long-term, these are usually unsustainable.  (Read: Why antidepressants stop working).
  • Withdrawal symptoms: When Effexor was initially released, medical professionals and marketers reported that the drug wasn’t associated with any significant discontinuation effects.  In fact, when users reported experiencing Effexor withdrawal symptoms, psychiatrists considered them to be misguided and/or that their underlying diagnosis was simply worsening.  These days, it is understood that Effexor has some of the most debilitating withdrawal symptoms compared to other antidepressants and that these symptoms can last for months after discontinuation.  Examples of such withdrawal symptoms include: anger, anxiety, brain zaps, dizziness, fatigue, and vomiting.
  • Worsening of anxiety: For a subset of users, Effexor may worsen underlying anxiety. Some people take Effexor and notice that it makes them feel more nervous and anxious than usual.  There is emerging evidence that some types of anxiety are caused by too much serotonin, and perhaps Effexor may exacerbate a serotonergic excess.  On the other hand, its ability to increase concentrations of norepinephrine, a stimulatory neurotransmitter, may also be responsible for an exacerbation of anxiety.

Effexor (Venlafaxine) for Anxiety Disorders: The Research

There is an extensive amount of scientific literature to support the usage of Effexor as a first-line intervention for anxiety disorders.  Nearly every study investigating venlafaxine as a treatment for anxiety disorders have noted its superior therapeutic efficacy when compared to a placebo.  Moreover, there don’t appear to be any limitations associated with research of venlafaxine as an anxiolytic – studies are well-designed, sample sizes are large, and the resulting evidence is robust.  Included below is a brief synopsis of the evidence.

2014: Venlafaxine extended-release treatment of hoarding disorder.

A study by Saxena and Sumner (2014) tested the efficacy of Effexor XR for the treatment of hoarding disorder.  Hoarding disorder is regarded as a subtype of anxiety disorder (and possible offshoot of OCD) in which individuals are compelled to save unnecessary items.  In previous research, the pharmacological intervention of Paxil (paroxetine) was found to be effective for reducing hoarding behaviors, but it was not well tolerated.

Researchers sought to determine whether Effexor XR may effectively mitigate hoarding behaviors without tolerability issues.  They recruited 24 individuals diagnosed with hoarding disorder (based on DSM-5 criteria) for an open-label trial.  It should be noted that, prior to this trial, all patients were free of psychiatric medications for at least 6 weeks.

All 24 participants were administered Effexor XR (once daily) for a period of 12 weeks.  No additional pharmacological or behavioral interventions were implemented throughout the study.  Measures of hoarding behavior were collected with the Saving Inventory-Revised (SI-R) and the UCLA Hoarding Severity Scale (UHSS); each assessment was administered before and after the 12-week trial.

Results indicated that symptoms of hoarding disorder were significantly attenuated with administration of Effexor XR.  Average scores on the SI-R decreased by 32% and average scores on the UHSS decreased by 36%.  Of the 23 individuals that finished the study, 70% were thought to derive significant therapeutic benefit from Effexor XR.  This provides preliminary evidence to suggest that Effexor XR may be a viable pharmaceutical for individuals with hoarding disorders, a subtype of anxiety disorder.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24722633

2009: Experience of the use of velaxin (venlafaxine) in anxious depression.

A study published by Il’ina (2009) examined the efficacy of venlafaxine among 30 individuals diagnosed with “anxious-depression.”  Of the 30 individuals, 7 were male and 23 were female, and 24 were treated on an inpatient basis, while 6 were treated as outpatients.  All patients received venlafaxine for an 8-week period at dosages ranging from 225 mg to 375 mg.

Measures were taken of mental state with various scales including the: CGI, HDRS, BDI, and HADS-21.  Results indicated that a majority of patients responded well to venlafaxine administered at intermediate doses.  Depressive symptoms, anxiety symptoms (especially somatic), as well as overall “mental state” – significantly improved for a majority of patients.  This highlights the efficacy of Effexor in treating depression with comorbid anxiety.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19234798

2008: Randomized placebo-controlled trial of escitalopram and venlafaxine XR in the treatment of generalized anxiety disorder.

Researchers Bose, Korotzer, and Gommoll (2008) documented the effects of Effexor XR and Lexapro for the treatment of generalized anxiety disorder.  They recruited a large number of participants, each of which were diagnosed with generalized anxiety (based on DSM-IV criteria).  The participants were set to receive either: Lexapro (10 to 20 mg per day), Effexor XR (75 to 225 mg per day), or a placebo (daily) – for a term of 8-weeks.

The study was randomized, double-blinded, and placebo-controlled.  Throughout the trial, severity of generalized anxiety was measured with the Hamilton Anxiety Scale (HAM-A).  The chief parameter for determining efficacy of each intervention was the average change in HAM-A scores after the 8-week term compared to baseline.

Results suggested that all individuals receiving the Effexor XR and Lexapro exhibited significantly reduced symptoms of generalized anxiety disorder after 8-weeks (as evidenced by the HAM-A).  Researchers suggested that both treatments were effective and well-tolerated for the treatment of generalized anxiety disorder.  However, fewer tolerability issues were reported among Lexapro users.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18050245

2007: Efficacy and safety of extended-release venlafaxine in the treatment of generalized anxiety disorder in children and adolescents: two placebo-controlled trials.

A trial conducted by Rynn et al. (2007) analyzed the safety and efficacy of Effexor XR as a treatment for generalized anxiety disorder (GAD) among children and adolescents.  Although there was evidence to suggest that Effexor was an effective and safe anxiolytic for adults with GAD, additional research was necessary to establish its safety and efficacy among younger individuals.  Researchers recruited 320 individuals (between 6 and 17 years of age) who were diagnosed with generalized anxiety disorder (via the DSM-IV criteria).

Of the 320 participants, 157 received Effexor XR while the remaining 163 received a placebo for 8-weeks.  Anxiety severity was measured based on 9 items from the Schedule For Affective Disorders and Schizophrenia for School-Age Children scale.  Secondary measures included the Pediatric Anxiety Scale and Hamilton Anxiety Scale (HAM-A).

Efficacy was determined based on average change in anxiety scores from baseline through 8-weeks.  Results demonstrated that those receiving Effexor XR significantly improved in both primary and secondary measures of anxiety after 8-weeks.  Though there were some unwanted adverse effects (e.g. somnolence, cholesterol increases, height/weight changes) – researchers concluded that Effexor XR was effective and well-tolerated for pediatric GAD.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17267793

2007: Venlafaxine extended release (XR) in the treatment of panic disorder.

In 2007, a report published by Kjernisted and McIntosh documented the efficacy of Effexor XR as an antipanic agent.  Researchers noted that Effexor XR appears to effectively reduce panic attacks among those diagnosed with panic disorder, regardless of whether administered over a short or long-term.  They also mentioned that in 12-week trials, Effexor XR was superior in efficacy to a placebo in facilitation of a “panic-free” state.

It was highlighted that relapses among those taking Effexor XR for panic disorder were significantly lower than those taking a placebo over the course of 6 months.  Evidence from this report suggests that Effexor XR significantly improves quality of life and overall functionality among those diagnosed with panic disorder.  Additionally, there were no significant issues with the tolerability of Effexor XR among those treated over a 6-month term.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18360616

2007: Extended-release formulation of venlafaxine in the treatment of post-traumatic stress disorder.

There is some evidence to suggest that Effexor is an effective intervention for the treatment of PTSD.  A report published by Pae et al. (2007) suggested that the pathophysiology of PTSD is associated with dysfunction of serotonin and norepinephrine.  In this report, researchers speculated that Effexor administration may normalize monoaminergic dysfunction associated with PTSD.

It was noted that in 2 randomized, placebo-controlled, double-blinded trials – Effexor demonstrated short-term and long-term efficacy for the treatment of PTSD symptoms.  Due to the limited research of Effexor as a treatment for PTSD, it is unclear as to whether it can be considered therapeutically effective.  That said, authors of this review hypothesize a therapeutic role of Effexor XR to mitigate severity of PTSD.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17563244

2006: Treatment of anxiety disorders with venlafaxine XR.

A report by Thase (2006) discussed the usage of Effexor XR as a treatment for anxiety disorders.  In the report, it was noted that following the introduction of an XR (extended-release) format of venlafaxine in 1997, the drug received approval as a treatment for several subtypes of anxiety disorders including: generalized anxiety disorder (GAD), panic disorder, and social phobia.  Thase highlighted evidence to suggest that Effexor XR was also likely effective as a treatment for PTSD and OCD.

Upon comparison to SSRIs, tolerability of Effexor XR is considered similar.  A few potentially unwanted noradrenergic side effects such as dry mouth, constipation, and hypertension – may occur among a subset of users.  That said, it was concluded that Effexor XR was an effective, tolerable treatment for a myriad of anxiety disorders.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16533131

2004: Efficacy of Venlafaxine ER in patients with social anxiety disorder: a double-blind, placebo-controlled, parallel-group comparison with paroxetine.

A large-scale trial conducted by Allgulander et al. (2004) assessed the anxiolytic efficacy of Effexor XR among individuals diagnosed with social anxiety disorder.  The study was considered short-term, placebo-controlled, double-blinded, and involved a parallel-group comparison of individuals treated with Paxil (paroxetine).  Researchers recruited a total of 434 participants and assigned them to receive one of three treatments: Effexor XR (75-225 mg/day), Paxil (20-50 mg/day), or the placebo (daily) – for a period of 12-weeks.

To gauge the efficacy of the three interventions (Effexor XR, Paxil, placebo), participant anxiety levels were measured with the Liebowitz Social Anxiety Scale.  Secondary measures were also collected via a patient-rated social phobia inventory.  Results indicated that those receiving the Effexor XR experienced significant reduction in symptoms of social anxiety disorder compared to the placebo; this finding held true across primary (Liebowitz scale) and secondary (patient-rated inventories) measures.

Individuals receiving the Paxil also experienced a significant reduction in symptoms of social anxiety as compared with the placebo – across both primary and secondary measures.  There were no significant differences in anxiolytic benefit among those taking Effexor XR compared to those taking Paxil.  Both Effexor XR and Paxil were considered safe, effective, and well-tolerated – providing additional evidence to support the usage of Effexor XR for social anxiety disorder.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15303242

2004: Venlafaxine in the treatment of anxiety disorders.

A paper published in 2004 by Katzman discussed Effexor XR as a pharmacological intervention for the treatment of anxiety disorders.  The author noted that Effexor XR exhibits unique pharmacodynamics in that it acts as a dual-reuptake inhibitor, simultaneously targeting both serotonin and norepinephrine.  Furthermore, it was mentioned that Effexor XR appears to provide clinically significant anxiety reduction among those with various anxiety disorders – as evidenced by controlled trials.

Specifically, controlled trials demonstrate Effexor XR’s therapeutic efficacy as a treatment for: generalized anxiety disorder (GAD), OCD, panic disorder, PTSD, and social anxiety disorder (SAD).  The author highlights the fact that Effexor XR appears to be safe and well-tolerated.  For this reason, Effexor XR should be considered an efficacious alternative to SSRIs for the treatment of anxiety disorders.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15853535

2003: Venlafaxine in treatment-resistant obsessive-compulsive disorder.

It is documented that up to 40% of individuals diagnosed with OCD derive insignificant therapeutic benefit from SSRIs.  Although SSRIs are an effective first-line option, other pharmacological options are necessary to treat the 40% of non-responders.  For this reason, researchers Hollander et al. (2004) analyzed the efficacy of Effexor, an SNRI as an alternative treatment for OCD.

A total of 39 individuals diagnosed with OCD (via DSM-IV criteria) were recruited for a trial.  Of the 39 individuals participating, 29 were noted as exhibiting treatment-resistant OCD (they didn’t respond to SSRI interventions).  Researchers collected measures of OCD severity at baseline using the CGI-IS (Clinical Global Impressions-Improvement Scale), as well as after treatment.

Among the 39 participants administered Effexor, a total of 27 experienced sustained OCD improvement.  Among the 29 individuals with treatment-resistant OCD, a total of 22 derived significant benefit from the Effexor treatment.  Researchers concluded that Effexor may be an effective treatment for OCD, even among individuals who derived no symptomatic improvement from previously administered SSRIs.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12755657

2002: Venlafaxine ER as a treatment for generalized anxiety disorder in older adults: pooled analysis of five randomized placebo-controlled clinical trials.

It was known that Effexor XR is a safe, effective treatment for generalized anxiety disorder among adults, but safety and efficacy haven’t been specifically investigated among older adults.  An analysis published in 2002 by Katz et al. assessed the safety and efficacy of Effexor XR as a treatment for generalized anxiety disorder among older patients.  They reviewed evidence from 5 placebo-controlled, double-blind, randomized, parallel-group, multicenter trials to determine Effexor XR’s safety and efficacy among 1,839 older individuals.

Efficacy of Effexor XR was determined based on Hamilton Rating Scale for Anxiety (HAM-A) measures.  Of the 1,839 participants, just 5% were over the age of 65, therefore most were not considered “elderly.”  Doses of Effexor XR administered ranged from 37.5 to 225 mg per day and were compared with a placebo for a duration of 8-weeks (in 3 studies) and 24-weeks (in 2 studies).

Results indicated that age of the patient didn’t affect the efficacy of Effexor XR as a treatment for generalized anxiety disorders.  Nearly 66% of patients were considered responders to Effexor XR, whereas only 41% responded to the placebo; these percentages are nearly identical to those seen in studies of younger adults.  Researchers concluded that Effexor XR is safe and well-tolerated as a treatment for generalized anxiety disorder, regardless of a user’s age (e.g. young adult vs. older adult).

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12028242

2002: Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder: a preliminary single-blind, 12-week, controlled study.

A trial conducted by Albert et al. (2002) assessed the efficacy of Effexor compared to clomipramine (a tricyclic antidepressant) for the treatment of OCD.  For the trial, researchers recruited a total of 73 patients that had been diagnosed with OCD (based on DSM-IV criteria).  Of the 73 participants, a total of 26 received Effexor (225-350 mg/day) and 47 received clomipramine (150-225 mg/day) for a duration of 12 weeks.

It should be noted that all participants hadn’t taken any psychiatric medication for at least 2 months prior to enrolling for the study.  To determine efficacy of the Effexor and clomipramine for the treatment of OCD, measures were collected with the YBOCS (Yale-Brown Obsessive Compulsive Scale) and CGI-S (Clinical Global Impressions-Scale).  A total of 25 individuals taking Effexor completed the trial, whereas 40 individuals taking clomipramine finished the full 12-week trial.

Individuals taking both the Effexor and clomipramine exhibited significant reductions in symptoms of OCD by the end of 12-weeks.  There appeared to be no differences in efficacy between the Effexor and clomipramine, but significantly more adverse effects were reported among those taking the clomipramine compared to those taking Effexor.  Results suggest that Effexor may be equally as effective as clomipramine for the treatment of OCD with a favorable side effect profile by comparison.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12444814

2001: Venlafaxine extended release (ER) in the treatment of generalized anxiety disorder: twenty-four-week placebo-controlled dose-ranging study.

A study conducted by Allgulander, Hackett, and Salinas (2001) documented the safety and efficacy of Effexor XR as a treatment for generalized anxiety disorder (GAD).  For the study, researchers recruited 541 individuals (ages 18 to 86) for a placebo-controlled, double-blinded, fixed-dose trial.  Individuals were set to receive either: fixed doses of Effexor XR (37.5 mg, 75 mg, 150 mg – per day) or a placebo – for a period of 24 weeks.

Results indicated that all three fixed doses of Effexor XR was significantly more effective than the placebo as a treatment for generalized anxiety disorder.  Superior anxiolytic efficacy compared to the placebo was noted after just 2 weeks of administration.  The 37.5 mg dose failed to sustain superior anxiolytic efficacy over the placebo for the entire 6 months.

However, the two higher doses of 75 mg and 150 mg maintained superior anxiolytic efficacy over the placebo for the entire 6-month duration after the second week.  Upon comparison of groups receiving fixed doses of Effexor XR and the placebo, no significant differences in discontinuation rates were noted; this implies favorable tolerability.  Researchers concluded that Effexor XR maintains therapeutic efficacy for at least 6-months as a treatment for generalized anxiety disorder.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11435263

2000: Venlafaxine XR in the treatment of anxiety.

In 2000, Hackett published a review of research involving Effexor XR as a treatment for anxiety disorders.  In previously published studies, Hackett noted that efficacy of Effexor XR as an anxiolytic was measured with various scales including the: Hamilton Rating Scale for Anxiety (HAM-A), Clinical Global Impressions scale (CGI), Hospital Anxiety and Depression scale, and more.  In all studies, safety and tolerability were properly assessed and adverse effects were reported.

Results from Hackett’s assessment indicated that Effexor XR was effective and well-tolerated among individuals diagnosed with generalized anxiety disorder.  It was mentioned that smaller-scale studies noted the efficacy of Effexor XR as a treatment for other subtypes of anxiety including: social anxiety disorder, OCD, and panic disorder.  This review concluded by stating that Effexor XR appears effective and safe as a short and/or long-term treatment for: chronic anxiety, comorbid anxiety and depression, as well as generalized anxiety disorder (GAD).

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11131468

1999: Venlafaxine extended release (XR) in the treatment of generalized anxiety disorder.

An article by Sheehan (1999) suggests that Effexor XR is an important therapeutic option for the treatment of anxiety disorders.  The researcher specifically documents Effexor XR as an effective intervention for generalized anxiety disorder (GAD) – as evidenced by improvements on the HAM-A (Hamilton Rating Scale for Anxiety).  Not only is Effexor XR an effective short-term anxiolytic intervention as seen in studies spanning for 8-weeks, but it appears to maintain its anxiolytic efficacy for up to 6 months.

Furthermore, one report suggested that Effexor XR was equally as effective as Buspar (an FDA approved anxiolytic) for the treatment of generalized anxiety disorder (GAD).  In fact, when compared head-to-head with Buspar, Effexor XR demonstrated superior efficacy in treating a subset of generalized anxiety disorder (GAD) symptoms.  The author (Sheehan) concluded that Effexor XR is effective and well-tolerated as a treatment for generalized anxiety disorder.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/10634352

1999: Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group.

A study by Silverstone and Ravindran (1999) compared the efficacy of Effexor XR to Prozac among individuals diagnosed with depression and anxiety.  They set-up a trial with a double-blinded, randomized, placebo-controlled design and recruited 359 patients that had been diagnosed with major depression and comorbid anxiety.  All patients were assigned to receive either: Effexor XR, Prozac, or a placebo – for a duration of 12 weeks.

To determine efficacy of pharmacological interventions, researchers measured severity of depression and anxiety throughout the trial with various scales such as the: Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions scale (CGI-S).  Results indicated that Effexor XR and Prozac were superior to the placebo for the treatment of depression (as evidenced by HAM-D scores).  Improvements in depressive symptoms began at week 2 and were maintained throughout the entirety of the 12-week trial duration.

That said, upon analysis of the HAM-D score improvements among those receiving Effexor XR and Prozac, only the Effexor XR improved a subset of the HAM-D measures, cumulatively known as the “depressed mood item.”  Perhaps most notable was the fact that HAM-A symptoms improved the most among those receiving the Effexor XR compared to the Prozac after 12-weeks.  This suggests that Effexor XR is safe, and likely better tolerated than Prozac for the treatment of major depression with comorbid anxiety.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/10074873

1999: Venlafaxine XR therapy for major depression and anxiety disorders. The clinical implications that its advantages pose.

A report by Sussman highlights some potential advantages associated with using Effexor XR as a treatment for depression and anxiety disorders.  In the report, Sussman mentions that although antidepressants such as SSRIs which exhibit a highly-selective mechanism of action, and were initially thought to be advantageous over other agents, they may be inferior to dual-reuptake inhibitors such as Effexor XR in terms of efficacy and tolerability.  Like SSRIs, Effexor XR is capable of treating both severe depression and comorbid anxiety disorders.

In addition, Effexor XR appears to be faster-acting and isn’t associated with significant unwanted weight gain.  Moreover, the combination of superior tolerability, faster therapeutic action, the ability to simultaneously target both depression and anxiety, and low risk of contraindications – makes Effexor XR an ideal psychiatric treatment.  Based on this report, one could speculate that dual-reuptake inhibitors such as Effexor XR may be favorable over older agents such as SSRIs.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19667502

1998: A meta-analysis of the effects of venlafaxine on anxiety associated with depression.

It is understood that many individuals diagnosed with depression exhibit concomitant anxiety.  A meta-analysis by Rudolph, Entsuah, and Chitra (1998) elucidates the effects of Effexor for the treatment of comorbid anxieties among those with depression.  For this meta-analysis, researchers pooled evidence from 6 short-term trials of Effexor that collected data of participant depression with the Hamilton Rating Scale for Depression (HAM-D).

Retrospectively, researchers analyzed the HAM-D results and focused specifically on Anxiety/Somatization factor and Anxiety Psychic item scores.  Of the 6 studies included in this meta-analysis, a total of 3 were placebo-controlled and the remaining 3 were placebo and drug-controlled.  The researchers classified individuals with depression as having comorbid anxiety if their Anxiety Psychic item scores (from the HAM-D) were at least “2.”

Results indicated that individuals with depression and comorbid anxiety experienced a significant reduction in anxious symptoms compared to the placebo.  Reductions in anxiety were evidenced by significant decreases on the HAM-D Anxiety/Somatization factor and Anxiety Psychic item scores.  Significant improvements in anxiety scores occurred by week 3 of the study among those receiving Effexor.

All anxiolytic improvements were sustained for the entire 6 weeks of treatment, and in a longer study, for a span of 12 weeks.  Although Effexor is already a well-established antidepressant, this meta-analysis provides evidence to support its usage as a monotherapy for cases of depression with concomitant anxiety.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/9555599

1998: Efficacy of once-daily venlafaxine extended release (XR) for symptoms of anxiety in depressed outpatients.

Among the first investigations of Effexor XR as a treatment for anxiety was conducted in 1998 by Feighner, Entsuah, and McPherson.  In this report, researchers analyzed the effects of Effexor XR (75-225 mg/day) in 2 randomized, double-blinded, placebo-controlled trials.  Researchers specifically sought to determine how Effexor XR administration affected anxiety levels of those receiving it as a treatment for depression.

Specifically, researchers looked at Anxiety-Psychic Item scores on the HAM-D.  Participants with an Anxiety-Psychic Item score of at least “2” (at baseline) on the HAM-D were considered to have concomitant anxiety (along with their depression).  In the first study, Effexor XR appeared substantially more effective than a placebo by week 4 of administration.

In the second study, significant reductions in anxiety were noted from weeks 1 to 8.  Some adverse effects such as: dry mouth, dizziness, insomnia, nausea, and sleepiness were reported; leading to discontinuation in 11% of patients.  That said, this report provides evidence to support the usage of Effexor XR (75-225 mg/day) to attenuate symptoms of anxiety among individuals with major depression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/9476744

Verdict: Effexor is a highly effective treatment for anxiety

Nearly every published study analyzing the efficacy of Effexor as a treatment for anxiety has discovered it to be therapeutically effective.  In all published placebo-controlled studies, Effexor demonstrated superior anxiolytic efficacy over placebos.  Additionally, in drug-controlled studies, Effexor was found to be of equal efficacy to already-approved pharmaceutical agents such as Paxil, Buspar, and clomipramine for the treatment anxiety disorders.

In some cases, Effexor was better tolerated to already-approved agents and/or yielded greater improvement of anxious symptoms.  It is also necessary to note that certain studies found Effexor to be faster-acting than SSRIs, providing quicker therapeutic benefit to patients by comparison.  Moreover, many researchers speculate that its propensity to target both serotonin and norepinephrine reduces likelihood of adverse effects such as weight gain.

The FDA has approved Effexor for the treatment of various types of anxiety disorders including: generalized anxiety disorder (GAD), panic disorder, and social phobia.  Emerging evidence highlights the therapeutic potential of Effexor for the treatment of additional anxious subtypes including: hoarding disorder, OCD, and PTSD.  In fact, some trials suggest that Effexor is capable of improving OCD symptoms among individuals who derived no therapeutic benefit from a previous SSRI trial.

Additionally, Effexor appears to effectively treat cases of major depression with comorbid anxiety as a monotherapy; this may be advantageous to administration of multiple drugs simultaneously.  It is thought to have few interactions and is universally regarded as a “well-tolerated” anxiolytic.  The anxiolytic efficacy of Effexor appears to be significant over a short-term (4 to 8 weeks) and over a long-term (up to 12-months).

Although Effexor may not be an optimal intervention for all users, there is ample evidence to support its usage as a treatment for anxiety disorders.  Individuals who fail to derive benefit from SSRIs and/or are struggling with anxious-depression – may respond well to Effexor XR.  Effexor is well-researched and understood to be the only SNRI capable of attenuating both depressive and anxious symptoms.

Taking Effexor XR for Anxiety… A Personal Anecdote

I’ve had some experience testing the efficacy of Effexor XR for the treatment of anxiety – specifically generalized anxiety and social phobia.  I began taking Effexor at around the age of 15-16 and stayed on it for about a month or two.  During my entire Effexor XR trial, I was taking the 37.5 mg dosage as manufactured by Wyeth and found the experience to be horrendous.

Not only did it make me feel more depressed and suicidal, but it worsened my anxiety.  I ended up with severe brain fog, hot flashes, depersonalization, and felt as if I was living in a bad dream.  Between the temperature changes, the worsening of anxiety, and increasingly depressed mood – my experience with Effexor XR was nothing short of nightmarish.  Clearly, not everyone taking Effexor XR has such an awful experience of adverse effects and/or exacerbation of anxiety – many people find it highly beneficial.

However, I’d like to share my anecdote as evidence that not everyone with an anxiety disorder is guaranteed to respond favorably to Effexor.  The aforestated evidence from clinical trials document its anxiolytic efficacy, but this does not imply that it is clinically effective for all users.  Many psychiatric medications for anxiety disorders are are a neurochemical gamble.

Although the odds are technically in your favor that Effexor will improve an anxiety disorder (as supported by the research), favorable odds don’t equal universal efficacy and tolerability.  Looking back, I speculate that I reacted poorly to both the combined serotonergic and noradrenergic effects elicited by Effexor.  I believe its noradrenergic mechanism worsened my anxiety by making me feel jittery and as if I wanted to crawl out of my skin.

That said, I was taking a very low dose at just 37.5 mg.  At such a low dose, the serotonergic mechanism was likely having the greatest impact on my neurotransmission.  I speculate that this mechanism was a poor fit for my overall neurophysiology, especially considering that I hadn’t responded to any SSRI/SNRI (other than Paxil) that I tested.

Venlafaxine simply didn’t do the trick for me.  I felt like it jumbled up my neurotransmitters (more than they already were at the time), making me feel like a depersonalized, agitated, anxious, depressed, temperature-changing zombie.  Reflecting upon the experience, I now realize that my psychiatrist was trying to help, but we were simply playing another round of “antidepressant roulette” – and my brain lost the gamble (despite favorable odds suggested by the research).

Have you tried Effexor (Venlafaxine) for anxiety?

If you’ve tried Effexor XR for an anxiety disorder (or are currently taking it), share your experience in the comments section below.  Mention the particular type of anxiety you’re treating with Effexor XR, your dosage, as well as the total duration over which you’ve been taking it.  If you derived anxiolytic benefit from Effexor XR, document how long it took to fully “kick in” after you began taking it.

If you’re a long-term Effexor XR user, has the drug maintained its anxiolytic efficacy?  Have you had to increase the dosage as a result of dwindling anxiolytic efficacy over an extended duration?  If you’ve had to increase your dosage due to tolerance, note how long it took (e.g. 1 year).

To help others get a better idea of your situation, document how effective (subjectively) you perceive Effexor XR to be for anxiety (on a scale of 1 to 10) as well as whether you are taking it as a standalone treatment or as part of a medication cocktail. Have you noticed any unwanted side effects since taking Effexor XR?  Realize that for some users, Effexor is an immensely helpful anxiolytic, while for others (like myself), it may be nothing more than an ineffective nightmare.

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{ 2 comments… add one }
  • PersonalAnectotemonsiuer February 28, 2016, 9:34 pm

    Increased anxiety at dose of 225 mg and most likely even less. It was extremely helpful for cognition however. Worked against sluggish cognitive tempo and being able to keep more than one number, or variable in the head. Maybe I could have kept it if there was a more pronounced opioid-mechanism… really sh*tty it got to this.

  • Jim September 23, 2016, 10:11 am

    I have been on Effexor XR, 75 mgs for only 5 weeks but I can already say its the most effective medication I’ve ever been on. I’ve been on medication the past 11 years for clinical depression, severe GAD, and ritualistic OCD. My other medications, Lexapro and Zoloft, worked fine for my depression but not as well on the anxiety side.

    Even at the full doses. I’m amazed that I’m doing better on the starting dose of Effexor than I was on the full doses of the others. And it’s not causing the lack of libido like the others did. I felt it start working after about a week and really kick in after 3 weeks. The only side effect I’m still dealing with is that its put me in a slightly hypomanic state.

    A little too hyper and energetic with some agitation. It was troublesome during weeks 3 and 4 but has started to dissipate this past week. I’m assuming it will continue to dissipate as my body is still in the adjustment phase. Overall, I’m extremely happy on how much better it is working on my anxiety than the other medications I was on.

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