Venlafaxine – StatPearls – NCBI Bookshelf

Continuing Education Activity

Venlafaxine is FDA approved to treat and manage symptoms of depression, social anxiety disorder, and cataplexy. Off-label, venlafaxine can be used for attention deficit disorder, fibromyalgia, diabetic neuropathy, complex pain syndromes, hot flashes, migraine prevention, post-traumatic stress disorder, obsessive-compulsive disorder, and premenstrual dysphoric disorder. Venlafaxine may be used independently or as part of combination therapy with other drugs. This activity outlines the indications, mechanism of action, administration methods, significant adverse effects, contraindications, toxicity, and monitoring, of venlafaxine so providers can direct patient therapy where it is indicated as part of the interprofessional team.

Objectives:

• Identify the approved and off-label indications for venlafaxine.

• Describe the adverse effects associated with venlafaxine, including the FDA black-box warning.

• Summarize the relevant drug-drug interactions of venlafaxine.

• Explain the importance of collaboration and coordination among the interprofessional team and how it can enhance patient care with venlafaxine therapy to improve patient outcomes for patients who have depression and related conditions for which it is indicated.

Access free multiple choice questions on this topic.

Indications

The prevalence of mental disorders in the United States is approximately 30 percent. The global burden of disease statistics shows that four of the ten most important causes of disease worldwide are psychiatric in origin. The pathophysiology behind psychiatric disorders is the imbalance of the complex neurotransmitter system in the brain.  The mainstay of treatment for depression and anxiety has been therapies to modulate these neuron transmitters, including selective serotonin reuptake inhibitors (SSRI), mixed norepinephrine/serotonin reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), and monoamine oxidase inhibitors (MAOI).  This article will focus on venlafaxine, which belongs to the class of antidepressants called serotonin-norepinephrine reuptake inhibitors (SNRIs).[1]

Venlafaxine is FDA approved to treat and manage symptoms of depression, social anxiety disorder,  and cataplexy. Off-label, venlafaxine can be used for attention deficit disorder, fibromyalgia, diabetic neuropathy, complex pain syndromes, hot flashes, migraine prevention, post-traumatic stress disorder, obsessive-compulsive disorder, and premenstrual dysphoric disorder.  Venlafaxine may be used independently or as part of combination therapy with other drugs.[2]

Mechanism of Action

Venlafaxine works by increasing serotonin levels, norepinephrine, and dopamine in the brain by blocking transport proteins and stopping their reuptake at the presynaptic terminal. This action leads to more transmitters available at the synapse and ultimately increases the stimulation of postsynaptic receptors. SNRIs act primarily upon serotonergic and noradrenergic neurons but have little or no effect upon cholinergic or histaminergic receptors. Venlafaxine is a bicyclic phenylethylamine compound.[3] Venlafaxine is a more potent inhibitor of serotonin reuptake than norepinephrine reuptake. Venlafaxine is essentially a selective serotonin reuptake inhibitor at 75 mg, and with higher doses such as 225 mg/day, it has significant effects on the norepinephrine transporter in addition to serotonin.

Administration

Venlafaxine is prescribed only for those 18 years and older and should not be used in children under 18. Venlafaxine should be taken with food, and patients should not take it with alcohol as combining alcohol and venlafaxine can lead to increased sedation. 

Venlafaxine comes in an oral tablet and an oral capsule. The oral tablets come in immediate-release (25 mg, 37.5 mg, 50 mg, 75 mg and 100 mg) and extended-release forms (37.5 mg, 75 mg, 150 mg, and 225 mg.) The immediate-release tablet can be cut or crushed, but the extended-release tablet may not be. Treatment for depression for the immediate release oral table typically starts at 75 mg total per day, given in two or three divided doses. [4] Dosage can increase to 150 mg per day, with a maximum dose of 375 mg per day. The typical starting dose of the extended-release oral tablet is 75 mg per day, taken as a single dose in the morning or evening. This dose can be increased by 75 mg every four days until reaching the maximum dose of 225 mg per day.

Adverse Effects

Venlafaxine causes a lower frequency of anticholinergic, sedating, and cardiovascular side effects but a higher incidence of gastrointestinal complaints, sleep impairment, and sexual dysfunction than TCAs. Additionally, venlafaxine may impair sexual function, resulting in diminished libido, impotence, or difficulty achieving orgasm. Sexual dysfunction frequently results in noncompliance and should be asked about specifically. Sexual dysfunction can sometimes be ameliorated by lowering the dose or instituting drug-free weekends and holidays in appropriate patients. Some patients find withdrawal symptoms uncomfortable.[5]  

Common side effects include: 

• Headache

• Nausea

• Insomnia, dizziness, hypotension, anorexia, somnolence

• Xerostomia

• Asthenia

• HTN

• Impotence, decreased libido, and/or anorgasmia

• Constipation

• Weight loss

• Abnormal dreams

• Diarrhea, abdominal pain

• Blurred vision

• Anxiety, tremor

• Hypercholesterolemia

• Hyponatremia

• Serotonin syndrome[6]

• Seizures

There is an FDA black box warning against venlafaxine as it can increase suicidality, cause depression exacerbation, hypomania/mania, and serotonin syndrome. Venlafaxine can also cause abnormal bleeding, altered platelet function, and anaphylaxis/anaphylactoid reaction. Venlafaxine can cause fatal skin conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme. Venlafaxine can also cause deterioration of glaucoma angle closure and seizures.[7] Venlafaxine has implications linking it to SIADH, HTN, arrhythmia, interstitial lung disease, eosinophilic pneumonia, pancreatitis, and hepatotoxicity. One main concern with SSRIs and SNRIs is the risk of serotonin syndrome, thought to result from hyperstimulation of brainstem 5HT-1A receptors.[8]

Contraindications

Contraindications to venlafaxine include concurrent use of monoamine oxidase inhibitors. Clinicians should not use venlafaxine if there is a history of anaphylaxis, and caution is necessary when combining venlafaxine with other serotonin modulators. Venlafaxine should be used cautiously with other sedating medications such as CNS depressants and alcohol use. Venlafaxine is contraindicated if it causes worsening suicidal ideation, depression, anxiety, and psychosis. Caution is advisable in heart failure patients, hyperthyroidism, and those with recent myocardial infarctions as it can raise blood pressure and increase heart rate. Venlafaxine raises the risk of seizures, and prescribers should avoid the drug in patients with a seizure disorder.[9] Venlafaxine can cause pupillary dilation and block the flow of fluid in the eye, leading to increased ocular pressure. Patients with glaucoma should have their eye pressures regularly monitored while taking venlafaxine. Venlafaxine is contraindicated in patients with uncontrolled angle-closure glaucoma.  Venlafaxine is a category C pregnancy drug. Venlafaxine can potentially pass into breast milk and cause side effects in breastfed children and should not be used in pregnancy and breastfeeding.

Monitoring

Venlafaxine can interact with many other medications, vitamins, or herbs.[10] Concurrent use of these agents can cause dangerous effects and are contraindicated with venlafaxine. The following is a brief list of drug interactions with venlafaxine:

• Patients should not take venlafaxine with monoamine oxidase inhibitors (MAOIs), linezolid, and methylene blue.  

• Caution is necessary when using venlafaxine with other drugs that can increase serotonin levels, including SSRIs, SNRIs, and tramadol, as they can lead to life-threatening serotonin syndrome. Other drugs that can raise serotonin include triptans, such as sumatriptan, rizatriptan, and zolmitriptan.

• Venlafaxine should not be combined with drugs for weight loss, such as phentermine. Using venlafaxine with drugs like phentermine may result in excessive weight loss, serotonin syndrome, and heart problems such as tachycardia and hypertension. 

• Venlafaxine with cimetidine raises the risk of high blood pressure or liver disease.

• Venlafaxine with haloperidol raises the risk of QT prolongation.[11]

• Venlafaxine taken with warfarin and anti-inflammatory drugs such as aspirin, ibuprofen, naproxen (NSAIDs) increase the risk of bleeding.

• Ritonavir, clarithromycin, or ketoconazole can inhibit the breakdown of venlafaxine leading to venlafaxine accumulation in the body.  

• Venlafaxine, taken with zolpidem, lorazepam, and diphenhydramine, can lead to increased sedation. 

• Metoprolol may be less effective when taken with venlafaxine.

• Venlafaxine can cause false positives when testing the patient’s urine for phencyclidine (PCP) and amphetamine. This effect may remain for several days after stopping venlafaxine.

Toxicity

Venlafaxine oral tablet is prescribed for long-term treatment, and it comes with serious risks if not taken as prescribed or stop it abruptly. Abrupt cessation of venlafaxine can lead to serious adverse effects such as irritability, tiredness, restlessness, anxiety,  insomnia, trouble sleeping, nightmares, headache, sweating, dizziness, tingling, or “pins and needles” feeling, shaking, confusion, nausea, vomiting, or diarrhea.  Symptoms of an overdose of venlafaxine can include: tachycardia, unusual sleepiness, dilated pupils, seizures, vomiting, cardiac arrhythmias, hypotension, muscle aches or pains, or dizziness.

Severe toxicity of venlafaxine, especially when combined with other antidepressants such as SSRI, SNRI, or MAOI, can lead to serotonin syndrome. Serotonin syndrome is a possibly life-threatening condition associated with increased serotonergic activity in the central nervous system. Serotonin syndrome may present with a spectrum of clinical findings, including autonomic hyperactivity, mental status changes, and neuromuscular abnormalities. Serotonin syndrome characteristically presents with myoclonus, agitation, abdominal cramping, hyperpyrexia, hypertension, and potentially death. No laboratory tests exist to confirm the diagnosis as serotonin concentrations do not correlate clinically with symptoms. Hunter Toxicity Criteria Decision Rules can be used to form the diagnosis.[12] To meet the criteria, the patient must be taking a serotonergic agent and fulfill one of the following conditions patients must exhibit spontaneous clonus

• An inducible clonus must be present, plus agitation or diaphoresis

• The presence of ocular clonus plus agitation or diaphoresis

• Tremor with hyperreflexia

• Hypertonia with a temperature above 38 degrees C plus ocular clonus or inducible clonus

Management of serotonin syndrome involves prompt discontinuation of all serotonergic agents with supportive care aimed at normalizing hemodynamics. Patient sedation with benzodiazepines and serotonin antagonists may also be an option.[8] Cyproheptadine can be an option in the event of a failure with benzodiazepines and supportive care. Cyproheptadine is a histamine-1 receptor antagonist with nonspecific 5-HT1A and 5-HT2A antagonistic properties, with an initial dose of 8 mg. treatment with propranolol, bromocriptine, or dantrolene is not recommended. Serotonin syndrome symptoms usually resolve within 24 hours of discontinuation of the offending agent.

Enhancing Healthcare Team Outcomes

Interprofessional healthcare team members should check the patient’s blood pressure before starting the medication and, additionally, continue to monitor blood pressure while on venlafaxine. Patients on venlafaxine should also have their renal function, and lipid profiles monitored. Close monitoring of psychiatric disorders, including symptoms of suicidality, depression, mania, anxiety, or unusual behavior changes, is a necessary precaution. Exercise care when transitioning from or to monoamine oxidase inhibitors. Do not start venlafaxine within two weeks of stopping an MAOI, and MAOI therapy should not commence within seven days of stopping venlafaxine. Only through close monitoring of the patient can the adverse effects be avoided. This monitoring should have contributions from all clinicians (MDs, DOs, NPs, PAs), nursing staff, and pharmacists, who need to coordinate their activities and openly share patient information to drive therapeutic decisions, minimize adverse events, drug-drug interactions, and optimizing patient outcomes. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

Strawn JR, Geracioti L, Rajdev N, Clemenza K, Levine A. Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review. Expert Opin Pharmacother. 2018 Jul;19(10):1057-1070. [PMC free article: PMC6340395] [PubMed: 30056792]

2.

Safarova TP, Yakovleva OB, Sheshenin VS, Gavrilova SI. [Methods of augmentation of antidepressant therapy (on the model of complex therapy with the inclusion of actovegin) in gerontopsychiatric hospital]. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(6. Vyp. 2):55-63. [PubMed: 30346435]

3.

Saad MA, El-Sahar AE, Sayed RH, Elbaz EM, Helmy HS, Senousy MA. Venlafaxine Mitigates Depressive-Like Behavior in Ovariectomized Rats by Activating the EPO/EPOR/JAK2 Signaling Pathway and Increasing the Serum Estradiol Level. Neurotherapeutics. 2019 Apr;16(2):404-415. [PMC free article: PMC6554373] [PubMed: 30361931]

4.

Fava GA, Benasi G, Lucente M, Offidani E, Cosci F, Guidi J. Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review. Psychother Psychosom. 2018;87(4):195-203. [PubMed: 30016772]

5.

Ning J, Luo J, Meng Z, Luo C, Wan G, Liu J, Wang S, Lian X, Melgiri ND, Sun Y, Huang R. The efficacy and safety of first-line therapies for preventing chronic post-surgical pain: a network meta-analysis. Oncotarget. 2018 Aug 10;9(62):32081-32095. [PMC free article: PMC6112831] [PubMed: 30174798]

6.

Zhan Z, Cao CS, Huang L. Serotonin Syndrome Induced by a Single Dose of Venlafaxine and Magnesium Valproate. Psychiatr Danub. 2021 Summer;33(2):193-195. [PubMed: 34185746]

7.

Dubovicky M, Belovicova K, Csatlosova K, Bogi E. Risks of using SSRI / SNRI antidepressants during pregnancy and lactation. Interdiscip Toxicol. 2017 Sep;10(1):30-34. [PMC free article: PMC6096863] [PubMed: 30123033]

8.

Schoretsanitis G, Augustin M, Saßmannshausen H, Franz C, Gründer G, Paulzen M. Antidepressants in breast milk; comparative analysis of excretion ratios. Arch Womens Ment Health. 2019 Jun;22(3):383-390. [PubMed: 30116895]

9.

Gallagher HC, Gallagher RM, Butler M, Buggy DJ, Henman MC. Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev. 2015 Aug 23;2015(8):CD011091. [PMC free article: PMC6481532] [PubMed: 26298465]

10.

Woroń J, Siwek M, Gorostowicz A. Adverse effects of interactions between antidepressants and medications used in treatment of cardiovascular disorders. Psychiatr Pol. 2019 Oct 30;53(5):977-995. [PubMed: 31955180]

11.

Sertraline and venlafaxine: new indication. Prevention of recurrent depression: no advance. Prescrire Int. 2005 Feb;14(75):19-20. [PubMed: 15751171]

12.

Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Mar 15, 2023. Venlafaxine. [PubMed: 30000251]

Disclosure: Dharminder Singh declares no relevant financial relationships with ineligible companies.

Disclosure: Abdolreza Saadabadi declares no relevant financial relationships with ineligible companies.

Venlafaxine – StatPearls – NCBI Bookshelf

Continuing Education Activity

Venlafaxine is FDA approved to treat and manage symptoms of depression, social anxiety disorder, and cataplexy. Off-label, venlafaxine can be used for attention deficit disorder, fibromyalgia, diabetic neuropathy, complex pain syndromes, hot flashes, migraine prevention, post-traumatic stress disorder, obsessive-compulsive disorder, and premenstrual dysphoric disorder. Venlafaxine may be used independently or as part of combination therapy with other drugs. This activity outlines the indications, mechanism of action, administration methods, significant adverse effects, contraindications, toxicity, and monitoring, of venlafaxine so providers can direct patient therapy where it is indicated as part of the interprofessional team.

Objectives:

• Identify the approved and off-label indications for venlafaxine.

• Describe the adverse effects associated with venlafaxine, including the FDA black-box warning.

• Summarize the relevant drug-drug interactions of venlafaxine.

• Explain the importance of collaboration and coordination among the interprofessional team and how it can enhance patient care with venlafaxine therapy to improve patient outcomes for patients who have depression and related conditions for which it is indicated.

Access free multiple choice questions on this topic.

Indications

The prevalence of mental disorders in the United States is approximately 30 percent. The global burden of disease statistics shows that four of the ten most important causes of disease worldwide are psychiatric in origin. The pathophysiology behind psychiatric disorders is the imbalance of the complex neurotransmitter system in the brain.  The mainstay of treatment for depression and anxiety has been therapies to modulate these neuron transmitters, including selective serotonin reuptake inhibitors (SSRI), mixed norepinephrine/serotonin reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), and monoamine oxidase inhibitors (MAOI).  This article will focus on venlafaxine, which belongs to the class of antidepressants called serotonin-norepinephrine reuptake inhibitors (SNRIs).[1]

Venlafaxine is FDA approved to treat and manage symptoms of depression, social anxiety disorder,  and cataplexy. Off-label, venlafaxine can be used for attention deficit disorder, fibromyalgia, diabetic neuropathy, complex pain syndromes, hot flashes, migraine prevention, post-traumatic stress disorder, obsessive-compulsive disorder, and premenstrual dysphoric disorder.  Venlafaxine may be used independently or as part of combination therapy with other drugs.[2]

Mechanism of Action

Venlafaxine works by increasing serotonin levels, norepinephrine, and dopamine in the brain by blocking transport proteins and stopping their reuptake at the presynaptic terminal. This action leads to more transmitters available at the synapse and ultimately increases the stimulation of postsynaptic receptors. SNRIs act primarily upon serotonergic and noradrenergic neurons but have little or no effect upon cholinergic or histaminergic receptors. Venlafaxine is a bicyclic phenylethylamine compound.[3] Venlafaxine is a more potent inhibitor of serotonin reuptake than norepinephrine reuptake. Venlafaxine is essentially a selective serotonin reuptake inhibitor at 75 mg, and with higher doses such as 225 mg/day, it has significant effects on the norepinephrine transporter in addition to serotonin.

Administration

Venlafaxine is prescribed only for those 18 years and older and should not be used in children under 18. Venlafaxine should be taken with food, and patients should not take it with alcohol as combining alcohol and venlafaxine can lead to increased sedation. 

Venlafaxine comes in an oral tablet and an oral capsule. The oral tablets come in immediate-release (25 mg, 37.5 mg, 50 mg, 75 mg and 100 mg) and extended-release forms (37.5 mg, 75 mg, 150 mg, and 225 mg.) The immediate-release tablet can be cut or crushed, but the extended-release tablet may not be. Treatment for depression for the immediate release oral table typically starts at 75 mg total per day, given in two or three divided doses. [4] Dosage can increase to 150 mg per day, with a maximum dose of 375 mg per day. The typical starting dose of the extended-release oral tablet is 75 mg per day, taken as a single dose in the morning or evening. This dose can be increased by 75 mg every four days until reaching the maximum dose of 225 mg per day.

Adverse Effects

Venlafaxine causes a lower frequency of anticholinergic, sedating, and cardiovascular side effects but a higher incidence of gastrointestinal complaints, sleep impairment, and sexual dysfunction than TCAs. Additionally, venlafaxine may impair sexual function, resulting in diminished libido, impotence, or difficulty achieving orgasm. Sexual dysfunction frequently results in noncompliance and should be asked about specifically. Sexual dysfunction can sometimes be ameliorated by lowering the dose or instituting drug-free weekends and holidays in appropriate patients. Some patients find withdrawal symptoms uncomfortable.[5]  

Common side effects include: 

• Headache

• Nausea

• Insomnia, dizziness, hypotension, anorexia, somnolence

• Xerostomia

• Asthenia

• HTN

• Impotence, decreased libido, and/or anorgasmia

• Constipation

• Weight loss

• Abnormal dreams

• Diarrhea, abdominal pain

• Blurred vision

• Anxiety, tremor

• Hypercholesterolemia

• Hyponatremia

• Serotonin syndrome[6]

• Seizures

There is an FDA black box warning against venlafaxine as it can increase suicidality, cause depression exacerbation, hypomania/mania, and serotonin syndrome. Venlafaxine can also cause abnormal bleeding, altered platelet function, and anaphylaxis/anaphylactoid reaction. Venlafaxine can cause fatal skin conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme. Venlafaxine can also cause deterioration of glaucoma angle closure and seizures.[7] Venlafaxine has implications linking it to SIADH, HTN, arrhythmia, interstitial lung disease, eosinophilic pneumonia, pancreatitis, and hepatotoxicity. One main concern with SSRIs and SNRIs is the risk of serotonin syndrome, thought to result from hyperstimulation of brainstem 5HT-1A receptors.[8]

Contraindications

Contraindications to venlafaxine include concurrent use of monoamine oxidase inhibitors. Clinicians should not use venlafaxine if there is a history of anaphylaxis, and caution is necessary when combining venlafaxine with other serotonin modulators. Venlafaxine should be used cautiously with other sedating medications such as CNS depressants and alcohol use. Venlafaxine is contraindicated if it causes worsening suicidal ideation, depression, anxiety, and psychosis. Caution is advisable in heart failure patients, hyperthyroidism, and those with recent myocardial infarctions as it can raise blood pressure and increase heart rate. Venlafaxine raises the risk of seizures, and prescribers should avoid the drug in patients with a seizure disorder.[9] Venlafaxine can cause pupillary dilation and block the flow of fluid in the eye, leading to increased ocular pressure. Patients with glaucoma should have their eye pressures regularly monitored while taking venlafaxine. Venlafaxine is contraindicated in patients with uncontrolled angle-closure glaucoma.  Venlafaxine is a category C pregnancy drug. Venlafaxine can potentially pass into breast milk and cause side effects in breastfed children and should not be used in pregnancy and breastfeeding.

Monitoring

Venlafaxine can interact with many other medications, vitamins, or herbs.[10] Concurrent use of these agents can cause dangerous effects and are contraindicated with venlafaxine. The following is a brief list of drug interactions with venlafaxine:

• Patients should not take venlafaxine with monoamine oxidase inhibitors (MAOIs), linezolid, and methylene blue.  

• Caution is necessary when using venlafaxine with other drugs that can increase serotonin levels, including SSRIs, SNRIs, and tramadol, as they can lead to life-threatening serotonin syndrome. Other drugs that can raise serotonin include triptans, such as sumatriptan, rizatriptan, and zolmitriptan.

• Venlafaxine should not be combined with drugs for weight loss, such as phentermine. Using venlafaxine with drugs like phentermine may result in excessive weight loss, serotonin syndrome, and heart problems such as tachycardia and hypertension. 

• Venlafaxine with cimetidine raises the risk of high blood pressure or liver disease.

• Venlafaxine with haloperidol raises the risk of QT prolongation.[11]

• Venlafaxine taken with warfarin and anti-inflammatory drugs such as aspirin, ibuprofen, naproxen (NSAIDs) increase the risk of bleeding.

• Ritonavir, clarithromycin, or ketoconazole can inhibit the breakdown of venlafaxine leading to venlafaxine accumulation in the body.  

• Venlafaxine, taken with zolpidem, lorazepam, and diphenhydramine, can lead to increased sedation. 

• Metoprolol may be less effective when taken with venlafaxine.

• Venlafaxine can cause false positives when testing the patient’s urine for phencyclidine (PCP) and amphetamine. This effect may remain for several days after stopping venlafaxine.

Toxicity

Venlafaxine oral tablet is prescribed for long-term treatment, and it comes with serious risks if not taken as prescribed or stop it abruptly. Abrupt cessation of venlafaxine can lead to serious adverse effects such as irritability, tiredness, restlessness, anxiety,  insomnia, trouble sleeping, nightmares, headache, sweating, dizziness, tingling, or “pins and needles” feeling, shaking, confusion, nausea, vomiting, or diarrhea.  Symptoms of an overdose of venlafaxine can include: tachycardia, unusual sleepiness, dilated pupils, seizures, vomiting, cardiac arrhythmias, hypotension, muscle aches or pains, or dizziness.

Severe toxicity of venlafaxine, especially when combined with other antidepressants such as SSRI, SNRI, or MAOI, can lead to serotonin syndrome. Serotonin syndrome is a possibly life-threatening condition associated with increased serotonergic activity in the central nervous system. Serotonin syndrome may present with a spectrum of clinical findings, including autonomic hyperactivity, mental status changes, and neuromuscular abnormalities. Serotonin syndrome characteristically presents with myoclonus, agitation, abdominal cramping, hyperpyrexia, hypertension, and potentially death. No laboratory tests exist to confirm the diagnosis as serotonin concentrations do not correlate clinically with symptoms. Hunter Toxicity Criteria Decision Rules can be used to form the diagnosis.[12] To meet the criteria, the patient must be taking a serotonergic agent and fulfill one of the following conditions patients must exhibit spontaneous clonus

• An inducible clonus must be present, plus agitation or diaphoresis

• The presence of ocular clonus plus agitation or diaphoresis

• Tremor with hyperreflexia

• Hypertonia with a temperature above 38 degrees C plus ocular clonus or inducible clonus

Management of serotonin syndrome involves prompt discontinuation of all serotonergic agents with supportive care aimed at normalizing hemodynamics. Patient sedation with benzodiazepines and serotonin antagonists may also be an option.[8] Cyproheptadine can be an option in the event of a failure with benzodiazepines and supportive care. Cyproheptadine is a histamine-1 receptor antagonist with nonspecific 5-HT1A and 5-HT2A antagonistic properties, with an initial dose of 8 mg. treatment with propranolol, bromocriptine, or dantrolene is not recommended. Serotonin syndrome symptoms usually resolve within 24 hours of discontinuation of the offending agent.

Enhancing Healthcare Team Outcomes

Interprofessional healthcare team members should check the patient’s blood pressure before starting the medication and, additionally, continue to monitor blood pressure while on venlafaxine. Patients on venlafaxine should also have their renal function, and lipid profiles monitored. Close monitoring of psychiatric disorders, including symptoms of suicidality, depression, mania, anxiety, or unusual behavior changes, is a necessary precaution. Exercise care when transitioning from or to monoamine oxidase inhibitors. Do not start venlafaxine within two weeks of stopping an MAOI, and MAOI therapy should not commence within seven days of stopping venlafaxine. Only through close monitoring of the patient can the adverse effects be avoided. This monitoring should have contributions from all clinicians (MDs, DOs, NPs, PAs), nursing staff, and pharmacists, who need to coordinate their activities and openly share patient information to drive therapeutic decisions, minimize adverse events, drug-drug interactions, and optimizing patient outcomes. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.

• Comment on this article.

References

1.

Strawn JR, Geracioti L, Rajdev N, Clemenza K, Levine A. Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review. Expert Opin Pharmacother. 2018 Jul;19(10):1057-1070. [PMC free article: PMC6340395] [PubMed: 30056792]

2.

Safarova TP, Yakovleva OB, Sheshenin VS, Gavrilova SI. [Methods of augmentation of antidepressant therapy (on the model of complex therapy with the inclusion of actovegin) in gerontopsychiatric hospital]. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(6. Vyp. 2):55-63. [PubMed: 30346435]

3.

Saad MA, El-Sahar AE, Sayed RH, Elbaz EM, Helmy HS, Senousy MA. Venlafaxine Mitigates Depressive-Like Behavior in Ovariectomized Rats by Activating the EPO/EPOR/JAK2 Signaling Pathway and Increasing the Serum Estradiol Level. Neurotherapeutics. 2019 Apr;16(2):404-415. [PMC free article: PMC6554373] [PubMed: 30361931]

4.

Fava GA, Benasi G, Lucente M, Offidani E, Cosci F, Guidi J. Withdrawal Symptoms after Serotonin-Noradrenaline Reuptake Inhibitor Discontinuation: Systematic Review. Psychother Psychosom. 2018;87(4):195-203. [PubMed: 30016772]

5.

Ning J, Luo J, Meng Z, Luo C, Wan G, Liu J, Wang S, Lian X, Melgiri ND, Sun Y, Huang R. The efficacy and safety of first-line therapies for preventing chronic post-surgical pain: a network meta-analysis. Oncotarget. 2018 Aug 10;9(62):32081-32095. [PMC free article: PMC6112831] [PubMed: 30174798]

6.

Zhan Z, Cao CS, Huang L. Serotonin Syndrome Induced by a Single Dose of Venlafaxine and Magnesium Valproate. Psychiatr Danub. 2021 Summer;33(2):193-195. [PubMed: 34185746]

7.

Dubovicky M, Belovicova K, Csatlosova K, Bogi E. Risks of using SSRI / SNRI antidepressants during pregnancy and lactation. Interdiscip Toxicol. 2017 Sep;10(1):30-34. [PMC free article: PMC6096863] [PubMed: 30123033]

8.

Schoretsanitis G, Augustin M, Saßmannshausen H, Franz C, Gründer G, Paulzen M. Antidepressants in breast milk; comparative analysis of excretion ratios. Arch Womens Ment Health. 2019 Jun;22(3):383-390. [PubMed: 30116895]

9.

Gallagher HC, Gallagher RM, Butler M, Buggy DJ, Henman MC. Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev. 2015 Aug 23;2015(8):CD011091. [PMC free article: PMC6481532] [PubMed: 26298465]

10.

Woroń J, Siwek M, Gorostowicz A. Adverse effects of interactions between antidepressants and medications used in treatment of cardiovascular disorders. Psychiatr Pol. 2019 Oct 30;53(5):977-995. [PubMed: 31955180]

11.

Sertraline and venlafaxine: new indication. Prevention of recurrent depression: no advance. Prescrire Int. 2005 Feb;14(75):19-20. [PubMed: 15751171]

12.

Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Mar 15, 2023. Venlafaxine. [PubMed: 30000251]

Disclosure: Dharminder Singh declares no relevant financial relationships with ineligible companies.

Disclosure: Abdolreza Saadabadi declares no relevant financial relationships with ineligible companies.

how to take drugs, effect, can you drink without a prescription and with alcohol

Medicine and health

Ekaterina Kushnir

treats anxiety disorder

I have generalized anxiety disorder.

For a long time I coped without pills and other help, but one day I got tired of constant anxiety and began to interfere with my normal life. As a result, I turned to a private psychiatrist.

The doctor prescribed an antidepressant from the SSRI group – these are selective serotonin reuptake inhibitors. Such drugs are the first thing prescribed in the treatment of depression and a number of other conditions, including my disease.

The doctor immediately warned me about some peculiarities associated with taking the drug. Some of them I then felt on myself. I think everyone who plans to be treated with antidepressants should know about them.

At the same time, it should be taken into account that most of the negative effects of therapy are temporary and not dangerous, and if they do not go away, one medicine can be replaced with another. Antidepressants help many people with mental disorders and other illnesses get rid of their symptoms and return to a full life, so you definitely should not be afraid of them. The main thing is to take such drugs when they are really needed: as prescribed by a competent doctor and under his control.

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Our articles are written with love for evidence-based medicine. We refer to authoritative sources and go to doctors with a good reputation for comments. But remember: the responsibility for your health lies with you and your doctor. We don’t write prescriptions, we give recommendations. Relying on our point of view or not is up to you.

Fact No. 1

Antidepressants may make symptoms worse at first

Antidepressants can increase anxiety in anxiety disorders, as well as cause irritability and agitation – the so-called causeless motor agitation, the inability to sit still. It’s not dangerous, but rather unpleasant. This condition is sometimes referred to as initial anxiety, that is, the anxiety of starting therapy. Up to 65% of people face it.

Antidepressant-induced anxiety syndrome – a systematic review in the British Journal of Psychiatry

There is also evidence that some classes of antidepressants, including SSRIs, may increase suicidal ideation in depression in young people aged 18 to 24 years. These data are not very reliable, and in older people, the risk of suicide no longer increases and even decreases.

Without treatment, depression is more likely to lead to suicidal thoughts, and in case of anxiety, you just need to prepare for such an effect, then it will be easier to survive the attacks.

The doctor told me that in the first two or three weeks there may be an increase in anxiety, but I did not take it too seriously.

Everything was fine for the first week. After about seven days, I became nervous and irritable. And then I woke up at night and after a while I felt an incomprehensible fear. My heartbeat increased, my head was spinning, my throat was constricted. Because of this, I felt a real panic – I spent the rest of the night fighting terrible thoughts, in the morning I got up completely broken.

8 myths about antidepressants

I never had such panic attacks before taking medication — my anxiety was background, general. I got scared and wrote to the doctor, who reassured me and said that it was not dangerous and would pass soon.

After that, I already expected these panic attacks, immediately tried to relax, calm down, remember that this was just a temporary effect of the drugs. And they ended faster, and then they completely disappeared.

My letter to a psychiatrist. I was scared: I expected an increase in background anxiety, but not panic attacks. I even thought about giving up the medicine

Fact No. 2

The effect of antidepressant treatment will not be immediate

Increase the dose of antidepressants gradually to reduce side effects. They usually start with the minimum, and then bring it up to the working one. For example, for SSRIs with the active ingredient “sertraline”, the working dose is from 100 mg per day. I started taking such a drug with 25 mg, and then gradually, in several steps, under the supervision of a doctor, raised the dose to 100 mg.

SSRI dosage – NHS

What doses of antidepressants will be optimal – an article in The Lancet

The process of reaching a working dose can take from two weeks to a month or more. It depends on the drug and its tolerance. I turned out to be sensitive to the medicine, it was hard for me to survive every increase in dosage: anxiety increased again, there were other side effects that then stopped. However, this is not the case for everyone, sometimes the process goes faster.

The full therapeutic effect, that is, the disappearance or a strong improvement in the symptoms of the disease, occurs some time after reaching the working dosage. As a rule, this is a week or two, although some positive changes may be earlier. For some people, this process stretches for a longer period: 6-12 weeks. Minimum initial doses of drugs usually do not work.

It is better to prepare for the fact that the symptoms of the disease will not disappear in the first weeks of treatment. And remember – this does not always mean that the drug needs to be changed, sometimes you just need to wait or further increase the dosage under the supervision of a doctor.

Fact No. 3

Antidepressants are usually taken in combination with other drugs

Another way to mitigate the side effects of antidepressants is to prescribe an additional drug along with them: for example, from the group of tranquilizers. Such drugs may have their own side effects, they should not be taken for a long time. Unlike antidepressants, some of them can be addictive. They are usually appointed for a month, but this period may be shorter or longer.

Antidepressants together with benzodiazepines work better for depression – BMJ magazine

My doctor prescribed a rather mild drug for me. However, he did not suit me. At first, it caused increased drowsiness: during the period of increased anxiety, it went away for a while, but then returned – even with half a pill I turned off and could sleep all day. And if I drank at night, I woke up with difficulty in the morning. The psychiatrist prescribed another medicine, but I could not buy it: the drug was not available in any pharmacy nearby.

As a result, I simply endured all the side effects of therapy – they were unpleasant, but tolerable. When discussing with the doctor, she called this option acceptable if the side effects of the second medicine only worsen the situation.

My prescriptions for drugs. I never used one, because there was no such medicine in pharmacies

Fact No. 4

Side effects are not always, but they are

Modern antidepressants, including SSRIs, are mild and have almost no side effects. Older drugs – tricyclic antidepressants and monoamine oxidase inhibitors – cause more side effects. Doctors usually use them when milder first-line drugs don’t work or when they can’t be prescribed.

Side effects of antidepressants – NHS

Side effects of different antidepressants – UpToDate

Side effects of antidepressants and their impact on the outcome of treatment of major depressive disorder – Nature

Selective reuptake inhibitors with erotonin – UpToDate

How to deal with side effects effects of antidepressants – advice from the Mayo Clinic staff

Choosing an SSRI drug does not guarantee the absence of side effects – many people tolerate treatment easily, but sometimes a change in drug may be necessary.

The first couple of weeks of taking there is a risk that the state of health will be so-so – it’s worth thinking about. It may be worth scheduling the start of therapy on vacation.

I work remotely, and it was easier for me: the first pill was taken on Saturday, I slept through the weekend. Then she continued to work, but refused any additional loads: housework, part-time jobs, training and everything else.

It was hard work: I wanted to sleep, then I began to worry and get distracted. I also had diarrhea, nausea, headaches, tremors, i.e. hand trembling, hot flashes, sweating, palpitations. At night, panic attacks began, in the morning I had difficulty getting up because I was in pain and dizzy.

There are mixed data on how common the side effects of antidepressants are. If we summarize them, then the numbers look something like this:

• nausea – about 25% feel it;
• diarrhea – it happens in 15% of people, and 5%, on the contrary, will have constipation;
• about 20% of people experience sweating and feeling hot;
• sexual dysfunction, decreased libido may occur in 80% of cases;
• insomnia – in 11% of cases;
• headache and dizziness – in about 10-11% of cases;
• weight gain – not all drugs give this effect. Some, on the contrary, can reduce weight. On my medicine, I lost 2 kilograms in the first month, despite the fact that I quit training due to poor health. True, then they returned back.

It can be seen that most side effects occur in less than half of the cases. In addition, in most cases they pass in the first weeks and are not dangerous.

Side effects not listed above are very rare. I was “lucky”, and I faced one such – a decrease in visual acuity. Once in the morning I noticed that I see worse without glasses. A little later, I realized that something was wrong with the glasses.

I wrote to the doctor, she replied that this happens, as a rule, is not dangerous and passes, but it is better to visit an ophthalmologist. I went to the ophthalmologist, everything was fine with my eyes, there was nothing terrible, but my vision really worsened – it was not a subjective feeling. On the right eye, it was -0.5 diopters, it became -0.75, and on the left eye it was -1.5, and it became -3.5.

I was offered to try changing the drug, but I decided to wait. Vision was then restored. I have not yet gone to the doctor to have it measured, but according to subjective feelings, it is at the same level as before: I am comfortable again in my glasses.

Side effects should not be tolerated – if something greatly worries, scares or interferes with life, it is better to tell the doctor right away. The psychiatrist will be able to determine whether the side effect of the drug is dangerous and whether it is worth continuing to take it. There are several antidepressants of the SSRI group, in addition, there are groups of drugs with a slightly different mechanism of action. As a rule, doctors manage to find a medicine that gives a good effect without side effects.

If there is no danger, the doctor can adjust the dose or increase it more gradually – this often helps to cope with unpleasant effects.

I wrote to the doctor again when my visual acuity decreased

Fact No. 5

Antidepressants need to be taken long term

Antidepressants are not drugs that you can stop drinking as soon as you get better. They are taken for a long time: usually from several months, less often several years.

Anxiety Therapy – UpToDate

For example, for generalized anxiety disorder, the duration of treatment is at least a year. Moreover, the date is not counted from the very beginning, but from the moment when a lasting effect appeared from the pills. In fact, they will have to be drunk for about 1.5 years – it depends on how long it takes to reach the working dosage of the medicine.

The cost of a package of the most famous antidepressant “Zoloft” is about 700 R, enough for about a month. That is, a course of therapy will cost about 10,000 R – maybe more or less, depending on which drug is selected.

Psychotherapy review – UpToDate

Another drug of the same group already costs more than 2000 R per pack. Source: rigla.ru

The cost of an appointment with a good psychiatrist in Moscow is 3000-5000 R. At first, you will need to visit him about once every 1-1.5 months, then less often.

You can apply to the psycho-neurological dispensary at the place of residence under compulsory medical insurance – it’s free. At the same time, they will not put you on psychiatric registration: it was canceled in 1993. People with disorders that do not threaten their lives or those around them are on consultative and diagnostic care. If you stop going to the doctor, he will not find out what happened: a person seeks help at will.

Psychotherapy, usually cognitive-behavioral, is also commonly prescribed to enhance and sustain the effects of antidepressants. In many cases, it improves the effectiveness of drugs, including depression and generalized anxiety disorder. An appointment with a psychotherapist in Moscow costs an average of 5000 R. For treatment, you will need about 10 sessions or more.

How psychotherapy works

Fact No. 6

Antidepressants should not be stopped abruptly

Antidepressants do not develop dependence. However, if you abruptly stop drinking them, there will be a withdrawal syndrome. This is felt as electric current discharges while moving or turning the head, headaches, dizziness, insomnia. Many people experience symptoms similar to the flu or an intestinal virus: low fever, diarrhea, general malaise, chills. Often there is anxiety, there are intrusive images.

Withdrawal symptoms after taking serotonin reuptake inhibitors – Journal of Clinical Psychiatry

How difficult it is to stop antidepressants – American Psychological Association

Stopping antidepressants in adults – UpToDate

for some reason they changed their minds about taking the pills or the term has expired treatment, they should be canceled only under the supervision of a doctor.

Antidepressant withdrawal occurs as gradually as the start of treatment. The dosage is slowly reduced, usually at this time again a cover-up drug is prescribed to alleviate side effects. As a rule, this is the same medicine that was at the beginning of the intake.

Withdrawal is usually harmless and resolves within the first weeks of stopping the drug. Sometimes even within a few days – it still depends on which medicine was prescribed. If severely disturbing symptoms appear during the withdrawal period, you should consult a doctor.

Fact No. 7

If you need to change the drug, everything will start over

It is far from always possible to immediately find the right antidepressant – sometimes the side effects do not go away and you need to take a new one.

Changing antidepressants in adults – UpToDate

Serotonin syndrome – MSD

Most often, it is started again with a small dosage, this delays the process of obtaining the effect of treatment. The new drug may also have side effects – the same or different. We will have to wait again until they pass.

You won’t be able to change the drug on your own, since all antidepressants are sold only by prescription – and that’s good. Switching from one drug to another can be dangerous if you do not know the characteristics of different groups of drugs.

For example, taking SSRIs is possible only some time after the withdrawal of antidepressants from the group of monoamine oxidase inhibitors – due to the risk of developing serotonin syndrome. This is a potentially fatal condition, accompanied by a change in mental state, high fever, increased muscle tone and other symptoms.

If the drug is changed correctly, there will be no dangerous negative effects, so consultation with a doctor is required.

How to choose a psychotherapist

Fact No. 8

Among antidepressants there are original drugs and generics

Preparations may be original or generic. Originals are drugs first released by some pharmaceutical company that have passed all clinical trials and checks. Generics are drugs with the same active ingredient from another pharmaceutical company, that is, copied from the original drug.

Theoretically, the action of generics should not differ from the action of original drugs. However, this is possible, since generics may contain other additional substances or the manufacturer may use other raw materials.

Due to my anxiety, I did not read anything in detail about specific drugs before I bought my first antidepressant in a pharmacy so as not to be scared and not think about taking it. I also didn’t think to ask the doctor about this question.

Psychoneurological complications after covid: memory problems and depression

As a result, I first bought a generic because it was in stock. Then it turned out that, after all, according to the experience of my psychiatrist, the original drug often gives fewer side effects and is better tolerated. As a result, I changed the generic to the original drug – and, indeed, the side effects softened.

In my subjective opinion, which is supported by some data, in the case of antidepressants and other psychotropic drugs, you should always choose the original medicine. Moreover, the cost of originals and generics is not always very different.

Originals and generics of some SSRIs

Sertraline

Original

Zoloft

Original price

About 700 R, tablets 100 mg

90 002 Generics

Serenata, Serlift

Cost of generics

500-600 R , tablets 100 mg

Escitalopram

Original

Cipralex

Original cost

3000 R, tablets 10 mg

Generics

Selektra, Elycea

Cost of generics

500-1300 R, tablets 10 mg

Fluoxetine

Original

Prozac

Original cost

About 350 R, tablets 20 mg

Generics

Profluzak, Fluoxetine

Cost of generics

100-200 R, tablets 20 mg

My pills: I bought several packs of Serenata at once, so one remained unclaimed ovannoy

Fact No. 9

Do not take alcohol along with antidepressants

Drinking alcohol while taking antidepressants may exacerbate unpleasant side effects. Also, alcohol is a depressant, that is, it has the opposite effect, and its intake can adversely affect the results of treatment.

Why you shouldn’t mix antidepressants and alcohol – Mayo Clinic

Alcohol is strictly forbidden to drink with some groups of antidepressants, for example, tricyclic antidepressants and monoamine oxidase inhibitors: combination with the latter, for example, can lead to an uncontrolled increase in pressure. MAO inhibitors in general require a special diet – it is unlikely that a doctor will prescribe such drugs as the first antidepressants, but if necessary, he will issue a list of what is allowed and prohibited.

With other antidepressants, moderate use may not be dangerous and may even pass without consequences, but doctors still recommend abstaining so as not to increase side effects and improve treatment outcome.

The main thing is not to temporarily stop taking the drug in order to drink. This can lead to the development of a withdrawal syndrome.

How I Treated Generalized Anxiety Disorder under CHI

Fact No. 10

Antidepressants are incompatible with certain drugs and have contraindications

It is important to tell your doctor what medications you are taking and what chronic illnesses you have. For example, SSRIs may not be suitable for epilepsy and bleeding disorders, and tricyclic antidepressants are usually not prescribed for those who have recently had a heart attack, suffer from glaucoma, or porphyria.

Antidepressant Warnings – NHS

Drug Compatibility Test – Drugs.com

It is also important to be careful if you are about to take any over-the-counter medicine. For example, ibuprofen, which people often take on their own to relieve pain and reduce fever. It should not be taken with SSRIs as it increases the risk of gastrointestinal side effects.

If it is not possible to consult a doctor before taking any medication, carefully read the instructions for it and your antidepressant. It is also worth informing all doctors who prescribe something to you during the therapy period about taking antidepressants.

Venlafaxine (Velafax, Velaxin, Newelong, Venlaxor)

Venlafaxine is FDA approved for the treatment of symptoms of depression, social anxiety disorder, and cataplexy. Without labeling, venlafaxine may be used for attention deficit disorder, fibromyalgia, diabetic neuropathy, complex pain syndromes, hot flashes, migraine prophylaxis, post-traumatic stress disorder, obsessive-compulsive disorder, and premenstrual dysphoric disorder. Venlafaxine can be used alone or as part of combination therapy with other drugs.

Indications for use

The prevalence of mental disorders in the United States is approximately 30 percent. Global burden of disease statistics show that four of the ten most important causes of disease worldwide are of psychiatric origin. The pathophysiology underlying mental disorders is an imbalance in the complex system of neurotransmitters in the brain. The mainstay of treatment for depression and anxiety has been modulation of these neurotransmitters, including selective serotonin reuptake inhibitors (SSRIs), mixed norepinephrine/serotonin reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). This article will focus on venlafaxine, which belongs to a class of antidepressants called serotonin-norepinephrine reuptake inhibitors (SNRIs).

Venlafaxine is FDA approved for the treatment of symptoms of depression, social anxiety disorder, and cataplexy. Without labeling, venlafaxine may be used for attention deficit disorder, fibromyalgia, diabetic neuropathy, complex pain syndromes, hot flashes, migraine prophylaxis, post-traumatic stress disorder, obsessive-compulsive disorder, and premenstrual dysphoric disorder. Venlafaxine can be used alone or as part of combination therapy with other drugs.

Mechanism of action

Venlafaxine increases the levels of serotonin, norepinephrine, and dopamine in the brain by blocking transport proteins and stopping their reuptake at the presynaptic terminal. This action leads to an increase in the number of transmitters available at the synapse and ultimately increases the stimulation of postsynaptic receptors. SNRIs act primarily on serotonergic and noradrenergic neurons, but have little effect on cholinergic or histaminergic receptors. Venlafaxine is a bicyclic compound of phenylethylamine. Venlafaxine is a more potent serotonin reuptake inhibitor than norepinephrine reuptake inhibitor. Venlafaxine is essentially a selective serotonin reuptake inhibitor at 75 mg, and at higher doses such as 225 mg/day it has a significant effect on the norepinephrine transporter in addition to serotonin.

Application

Venlafaxine causes a lower incidence of anticholinergic, sedative, and cardiovascular side effects, but a higher incidence of gastrointestinal complaints, sleep disturbance, and sexual dysfunction than TCAs. In addition, venlafaxine may impair sexual function, leading to decreased libido, impotence, or difficulty achieving orgasm. Sexual dysfunction often leads to non-compliance, which should be asked specifically. Occasionally, sexual dysfunction can be alleviated by lowering the dose or giving affected patients medication-free weekends and holidays. Some patients experience discomfort with withdrawal symptoms

Venlafaxine is available as oral tablets and capsules for oral administration. Tablets for oral administration are available in immediate release (25 mg, 37.5 mg, 50 mg, 75 mg and 100 mg) and extended release (37.5 mg, 75 mg, 150 mg and 225 mg) forms. a release tablet can be cut or crushed, but an extended release tablet cannot. Treatment of depression in the form of immediate-release oral tablets usually begins with a total dose of 75 mg per day given in two or three divided doses. The dosage may be increased up to 150 mg per day, with a maximum dose of 375 mg per day. A typical starting dose for extended release oral tablets is 75 mg per day, taken as a single morning or evening. This dose can be increased by 75 mg every four days until a maximum dose of 225 mg per day is reached.

Side effects

Venlafaxine causes a lower incidence of anticholinergic, sedative, and cardiovascular side effects, but a higher incidence of gastrointestinal complaints, sleep disturbance, and sexual dysfunction than TCAs. In addition, venlafaxine may impair sexual function, leading to decreased libido, impotence, or difficulty achieving orgasm. Sexual dysfunction often leads to non-compliance, which should be asked specifically. Occasionally, sexual dysfunction can be alleviated by lowering the dose or giving affected patients medication-free weekends and holidays. Some patients experience discomfort with withdrawal symptoms.

Common side effects include:

• Headache;
• Nausea;
• Insomnia, dizziness, hypotension, anorexia, drowsiness;
• xerostomia;
• Asthenia;
• HTN;
• impotence, decreased libido and/or anorgasmia;
• Constipation;
• Weight loss;
• abnormal dreams;
• diarrhea, abdominal pain;
• visual impairment;
• restlessness, tremor;
• hypercholesterolemia;
• Hyponatremia;
• Serotonin syndrome;
• Seizures.

The FDA alert contains a warning against venlafaxine because it may increase suicidality, exacerbate depression, hypomania, and serotonin syndrome. Venlafaxine can also cause abnormal bleeding, altered platelet function, and anaphylaxis/anaphylactoid reaction. Venlafaxine can cause fatal skin conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme. Venlafaxine can also cause worsening of glaucoma angle closure and convulsions. Venlafaxine has implications linking it to SIADH, HTN, arrhythmia, interstitial lung disease, eosinophilic pneumonia, pancreatitis, and hepatotoxicity. One of the major concerns with SSRIs and SNRIs is the risk of serotonin syndrome, which is thought to be the result of overstimulation of 5HT-1A receptors in the brainstem.

Contraindications

Contraindications to venlafaxine include concomitant use of monoamine oxidase inhibitors. Physicians should not prescribe venlafaxine if there has been a history of anaphylaxis, and caution is needed when combining venlafaxine with other serotonin modulators. Venlafaxine should be used with caution with other sedatives such as CNS depressants and with alcohol. Venlafaxine is contraindicated if it causes increased suicidal ideation, depression, anxiety, and psychosis. Caution is advised in patients with heart failure, hyperthyroidism, and patients with recent myocardial infarctions as it may increase blood pressure and increase heart rate. Venlafaxine increases the risk of seizures and prescribers should avoid taking the drug in patients with seizure disorders. Venlafaxine can cause pupillary dilation and block the flow of fluid in the eye, resulting in increased eye pressure. Patients with glaucoma should regularly monitor eye pressure while taking venlafaxine. Venlafaxine is contraindicated in patients with uncontrolled angle-closure glaucoma. Venlafaxine is a category C pregnancy drug. Venlafaxine has the potential to pass into breast milk and cause side effects in breastfed infants and should not be used during pregnancy and breastfeeding.

Monitoring

Venlafaxine may interact with many other medicines, vitamins, or herbs. The simultaneous use of these drugs can cause dangerous effects and is contraindicated for venlafaxine. The following is a summary of drug interactions with venlafaxine:

• Patients should not take venlafaxine with monoamine oxidase inhibitors (MAOIs), linezolid, and methylene blue;
• Caution is needed when using venlafaxine with other drugs that can increase serotonin levels, including SSRIs, SNRIs and tramadol, as they can lead to life-threatening serotonin syndrome. Other drugs that may increase serotonin levels include triptans such as sumatriptan, rizatriptan, and zolmitriptan;
• Venlafaxine should not be combined with weight loss drugs such as phentermine. The use of venlafaxine with drugs such as phentermine can lead to excessive weight loss, serotonin syndrome, and heart problems such as tachycardia and hypertension;
• Venlafaxine with cimetidine increases the risk of high blood pressure or liver disease;
• Venlafaxine with haloperidol increases the risk of QT interval prolongation;
• Venlafaxine, taken with warfarin and anti-inflammatory drugs such as aspirin, ibuprofen, naproxen (NSAIDs), increases the risk of bleeding;
• Ritonavir, clarithromycin, or ketoconazole may inhibit the breakdown of venlafaxine, leading to accumulation of venlafaxine in the body;
• Venlafaxine taken together with zolpidem, lorazepam and diphenhydramine may lead to increased sedation;
• Metoprolol may be less effective when taken with venlafaxine;
• Venlafaxine can cause false-positive results when testing a patient’s urine for phencyclidine (PCP) and amphetamine. This effect may persist for several days after venlafaxine is discontinued.

Toxicity

Venlafaxine oral tablets are prescribed for long-term treatment, and there are serious risks if not taken as directed or stopped abruptly. Stopping venlafaxine abruptly can lead to serious side effects such as irritability, fatigue, restlessness, anxiety, insomnia, sleep problems, nightmares, headache, sweating, dizziness, tingling or tingling, trembling, confusion, nausea , vomiting or diarrhea. Symptoms of an overdose of venlafaxine may include: tachycardia, unusual drowsiness, dilated pupils, convulsions, vomiting, heart rhythm disturbances, hypotension, muscle pain or dizziness.

Severe venlafaxine toxicity, especially when combined with other antidepressants such as SSRIs, SNRIs, or MAOIs, can lead to serotonin syndrome. Serotonin syndrome is a possibly life-threatening condition associated with increased serotonergic activity in the central nervous system. Serotonin syndrome can present with a range of clinical manifestations, including autonomic hyperactivity, mental status changes, and neuromuscular abnormalities. Serotonin syndrome is characterized by myoclonus, agitation, abdominal cramps, hyperpyrexia, hypertension, and possibly death. There are no laboratory tests to confirm the diagnosis because serotonin concentrations do not clinically correlate with symptoms. Hunter toxicity criteria decision rules can be used to make a diagnosis. To meet the criteria, the patient must be taking a serotonergic agent and meet one of the following conditions patients must have spontaneous clonus

• Inducible clonus must be present, as well as agitation or sweating;
• Presence of clonus in the eyes plus agitation or sweating;
• Tremor with hyperreflexia;
• Hypertension above 38 degrees Celsius plus ocular clonus or induced clonus.

Treatment of serotonin syndrome includes the immediate withdrawal of all serotonergic drugs with supportive therapy aimed at normalizing hemodynamics. Sedation of patients with benzodiazepines and serotonin antagonists may also be an option. Cyproheptadine may be an alternative when benzodiazepines and supportive therapy fail. Cyproheptadine is a histamine-1 receptor antagonist with non-specific 5-HT1A and 5-HT2A antagonistic properties, with an initial dose of 8 mg. treatment with propranolol, bromocriptine, or dantrolene is not recommended. Symptoms of serotonin syndrome usually resolve within 24 hours of stopping the irritating drug.

Article about Venlafaxine.

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