Drugs List

Therapeutic Indications

Uses

Prevention of relapse or recurrence of depressive illness
Treatment of depressive illness

Contraindications

Children under 18 years
Within 2 weeks of discontinuing MAOIs
Breastfeeding
Long QT syndrome
Torsade de pointes
Uncontrolled hypertension

Precautions and Warnings

Elderly
Family history of bipolar disorder
Family history of long QT syndrome
Patients under 25 years
Predisposition to haemorrhage
Predisposition to narrow angle glaucoma
Suicidal ideation
Aggression
Bipolar disorder
Coagulopathy
Dehydration
Diabetes mellitus
Electrolyte imbalance
Epileptic disorder
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
History of mania
History of seizures
History of torsade de pointes
Intraocular hypertension
Lactose intolerance
Pregnancy
Recent myocardial infarction
Renal impairment - glomerular filtration rate below 30ml/minute
Serious cardiac arrhythmias
Unstable cardiac disorder

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Correct electrolyte disorders before treatment
Patients at risk of suicide should be closely supervised
Reduce dose in patients with hepatic impairment
Reduce dose in patients with severe renal impairment
Advise patient ability to drive or operate machinery may be impaired
Oral solution contains parabens: Potential for delayed allergic reactions
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Consider monitoring ECG in patients at risk of QT prolongation
Discontinue treatment if patient develops seizures
May cause hyponatraemia
Monitor cholesterol and triglyceride levels
Monitor heart rate and blood pressure regularly
Monitor patient closely during titration of dose
Monitor patients at risk of glaucoma for increases in intraocular pressure
Monitor patients for adverse reactions including restlessness & agitation
Monitor patients for signs and symptoms of Serotonin Syndrome
Monitor serum electrolytes
When used with SSRIs, risk of Serotonin syndrome
Aggressive behaviour may occur
Consider dose reduction or discontinuation if serotonin syndrome suspected
Decreased salivary secretions may lead to dental caries
Do not increase dosage in patients who develop akathisia
Potential for increased risk of bleeding
Potential for withdrawal symptoms
May affect results of some laboratory tests
Avoid MAOIs for 7 days after discontinuing this drug
To discontinue, reduce dose gradually
Maintain treatment at the lowest effective dose
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patient on need for adequate dental hygiene & regular dental checks
Advise patient/carers to report signs of suicide ideation or behaviour

Close supervision is advised in all patients, in particular those at high risk, during early treatment and following dose changes.

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in children, adolescents and adult under 25 years, antidepressants may increase the risk of suicidal thoughts and self harm.

Other psychiatric conditions for which venlafaxine is prescribed can also be associated with an increased risk of suicide related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.

Increases in heart rate can occur, particularly at high doses. Caution should be exercised in patients whose underlying conditions might be compromised by increased heart rate.

Serotonin-norepinephrine reuptake inhibitors may cause symptoms of sexual dysfunction. There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite their discontinuation.

Pregnancy and Lactation

Pregnancy

Use venlafaxine with caution during pregnancy.

The manufacturer does not recommend using venlafaxine during pregnancy and that venlafaxine must only be administered to pregnant women if the expected benefits outweigh any possible risk. Animal studies have shown teratogenic effects, however human data is limited. Whilst the limited human data has shown no evidence of structural anomalies, developmental toxicity including spontaneous abortions, low birth weight, premature birth, neonatal serotonin syndrome, neonatal behavioural syndrome (withdrawal including seizures) and respiratory distress have been reported.

Persistent pulmonary hypertension (PPHN) in the newborn is also a potential risk. Whilst a link to venlafaxine has not been investigated, epidemiological data suggests an increased risk of PPHN following use of selective serotonin re-uptake inhibitors (SNRIs), particularly during late pregnancy. Due to their similar mechanism of action, a risk with venlafaxine cannot be ruled out. SNRIs may also increase the risk of postpartum haemorrhage within the month prior to birth.

Use of venlafaxine up until or shortly before birth can cause withdrawal effects or adaptation problems in the neonate. In the majority of cases, symptoms arise within 24 hours of delivery and include irritability, tremor, hypotonia, persistent crying, and difficulty in sucking or in sleeping. Complications requiring tube-feeding, respiratory support or prolonged hospitalisation have also been reported. There is an increased risk of postpartum haemorrhage following SNRIs exposure within the month prior to birth.

In patients established on venlafaxine prior to becoming pregnant, abrupt discontinuation should be avoided as this carries a higher risk of relapse. Ongoing management should balance potential risk to the foetus with potential risk to maternal health if treatment is discontinued/changed. Venlafaxine may be continued with caution in those at a significant risk of relapse. When managing new episodes of depression or anxiety during pregnancy, consider the use of psychological therapy where possible. Whilst no antidepressant is considered safe during pregnancy, alternative options with greater experience may be preferable.

Lactation

Venlafaxine is contraindicated in breastfeeding.

The manufacturer advises that the patient either discontinues venlafaxine or discontinues breastfeeding.

Venlafaxine and its active metabolite, O-desmethylvenlafaxine are excreted in human breast milk. There are reports of nursing infants experiencing crying, irritability and abnormal sleep patterns. Breastfed infants, especially newborn or preterm infants, should be monitored for excessive sedation and adequate weight gain if this drug is used during lactation (LactMed, 2022). Discontinuation symptoms have been reported after stopping breastfeeding.

Briggs (2015) notes that venlafaxine provides a relatively high infant dose compared to other antidepressants and that long-term effects on neurobehaviour and cognitive development have not been adequately studied. If used, the infant should be monitored for short-term adverse effects. Schaefer (2015) concludes that venlafaxine is tolerable if compellingly indicated, but that whenever possible, drugs of choice among the tricyclic antidepressants or selective serotonin re-uptake inhibitors should be used in preference.

Side Effects

Abnormal ejaculation
Abnormal liver function tests
Agitation
Agranulocytosis
Akathisia
Alopecia
Anaphylaxis
Anorgasmia
Apathy
Aplastic anaemia
Asthenia
Blood dyscrasias
Bruxism
Chills
Confusion
Constipation
Convulsions
Decreased appetite
Delirium
Depersonalisation
Diarrhoea
Disturbances in accommodation
Dizziness
Dream abnormalities
Dry mouth
Dyskinesia
Dystonia
Ecchymosis
Erectile dysfunction
Erythema multiforme
Extrapyramidal effects
Gastro-intestinal haemorrhage
Glaucoma (closed angle)
Hallucinations
Headache
Hepatitis
Hot flushes
Hypertension
Hyponatraemia
Hypotension
Impaired co-ordination
Impaired urination
Inappropriate secretion of antidiuretic hormone
Increase in muscle tone
Increase in serum cholesterol (transient)
Increased prolactin
Insomnia
Mania
Menorrhagia
Menstrual disturbances
Metrorrhagia
Mucous membrane bleeding
Mydriasis
Myoclonus
Nausea
Nervousness
Neuroleptic malignant syndrome
Neutropenia
Night sweats
Orgasmic dysfunction
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Photosensitivity
Pollakiuria
Postural hypotension
Prolongation of QT interval
Prolonged bleeding
Pruritus
Psychomotor restlessness
Pulmonary eosinophilia
Rash
Reduced libido
Rhabdomyolysis
Sedation
Serotonin syndrome
Stevens-Johnson syndrome
Suicidal tendencies
Sweating
Syncope
Tachycardia
Tardive dyskinesia
Taste disturbances
Thrombocytopenia
Tinnitus
Torsades de pointes
Toxic epidermal necrolysis
Tremor
Urinary retention
Urticaria
Vasodilatation
Ventricular fibrillation
Ventricular tachycardia
Visual disturbances
Vomiting
Weight changes
Yawning

Presentation

Standard release oral formulations of venlafaxine.

Drugs List

Therapeutic Indications

Uses

Prevention of relapse or recurrence of depressive illness
Treatment of depressive illness

Dosage

Treatment should be reassessed regularly on a case-by-case basis, taking into consideration the risk of relapse or recurrence of symptoms.

Dose increases should be made at 2 week intervals or more. In severe cases, doses may be increased more frequently but not less than every 4 days.

Antidepressive treatment should continue for at least six months following remission.

Adults

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Within 2 weeks of discontinuing MAOIs
Breastfeeding
Long QT syndrome
Torsade de pointes
Uncontrolled hypertension

Precautions and Warnings

Elderly
Family history of bipolar disorder
Family history of long QT syndrome
Patients under 25 years
Predisposition to haemorrhage
Predisposition to narrow angle glaucoma
Suicidal ideation
Aggression
Bipolar disorder
Coagulopathy
Dehydration
Diabetes mellitus
Electrolyte imbalance
Epileptic disorder
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
History of mania
History of seizures
History of torsade de pointes
Intraocular hypertension
Lactose intolerance
Pregnancy
Recent myocardial infarction
Renal impairment - glomerular filtration rate below 30ml/minute
Serious cardiac arrhythmias
Unstable cardiac disorder

Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Correct electrolyte disorders before treatment
Patients at risk of suicide should be closely supervised
Reduce dose in patients with hepatic impairment
Reduce dose in patients with severe renal impairment
Advise patient ability to drive or operate machinery may be impaired
Oral solution contains parabens: Potential for delayed allergic reactions
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Consider monitoring ECG in patients at risk of QT prolongation
Discontinue treatment if patient develops seizures
May cause hyponatraemia
Monitor cholesterol and triglyceride levels
Monitor heart rate and blood pressure regularly
Monitor patient closely during titration of dose
Monitor patients at risk of glaucoma for increases in intraocular pressure
Monitor patients for adverse reactions including restlessness & agitation
Monitor patients for signs and symptoms of Serotonin Syndrome
Monitor serum electrolytes
When used with SSRIs, risk of Serotonin syndrome
Aggressive behaviour may occur
Consider dose reduction or discontinuation if serotonin syndrome suspected
Decreased salivary secretions may lead to dental caries
Do not increase dosage in patients who develop akathisia
Potential for increased risk of bleeding
Potential for withdrawal symptoms
May affect results of some laboratory tests
Avoid MAOIs for 7 days after discontinuing this drug
To discontinue, reduce dose gradually
Maintain treatment at the lowest effective dose
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patient on need for adequate dental hygiene & regular dental checks
Advise patient/carers to report signs of suicide ideation or behaviour

Close supervision is advised in all patients, in particular those at high risk, during early treatment and following dose changes.

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in children, adolescents and adult under 25 years, antidepressants may increase the risk of suicidal thoughts and self harm.

Other psychiatric conditions for which venlafaxine is prescribed can also be associated with an increased risk of suicide related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.

Increases in heart rate can occur, particularly at high doses. Caution should be exercised in patients whose underlying conditions might be compromised by increased heart rate.

Serotonin-norepinephrine reuptake inhibitors may cause symptoms of sexual dysfunction. There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite their discontinuation.

Pregnancy and Lactation

Pregnancy

Use venlafaxine with caution during pregnancy.

The manufacturer does not recommend using venlafaxine during pregnancy and that venlafaxine must only be administered to pregnant women if the expected benefits outweigh any possible risk. Animal studies have shown teratogenic effects, however human data is limited. Whilst the limited human data has shown no evidence of structural anomalies, developmental toxicity including spontaneous abortions, low birth weight, premature birth, neonatal serotonin syndrome, neonatal behavioural syndrome (withdrawal including seizures) and respiratory distress have been reported.

Persistent pulmonary hypertension (PPHN) in the newborn is also a potential risk. Whilst a link to venlafaxine has not been investigated, epidemiological data suggests an increased risk of PPHN following use of selective serotonin re-uptake inhibitors (SNRIs), particularly during late pregnancy. Due to their similar mechanism of action, a risk with venlafaxine cannot be ruled out. SNRIs may also increase the risk of postpartum haemorrhage within the month prior to birth.

Use of venlafaxine up until or shortly before birth can cause withdrawal effects or adaptation problems in the neonate. In the majority of cases, symptoms arise within 24 hours of delivery and include irritability, tremor, hypotonia, persistent crying, and difficulty in sucking or in sleeping. Complications requiring tube-feeding, respiratory support or prolonged hospitalisation have also been reported. There is an increased risk of postpartum haemorrhage following SNRIs exposure within the month prior to birth.

In patients established on venlafaxine prior to becoming pregnant, abrupt discontinuation should be avoided as this carries a higher risk of relapse. Ongoing management should balance potential risk to the foetus with potential risk to maternal health if treatment is discontinued/changed. Venlafaxine may be continued with caution in those at a significant risk of relapse. When managing new episodes of depression or anxiety during pregnancy, consider the use of psychological therapy where possible. Whilst no antidepressant is considered safe during pregnancy, alternative options with greater experience may be preferable.

Lactation

Venlafaxine is contraindicated in breastfeeding.

The manufacturer advises that the patient either discontinues venlafaxine or discontinues breastfeeding.

Venlafaxine and its active metabolite, O-desmethylvenlafaxine are excreted in human breast milk. There are reports of nursing infants experiencing crying, irritability and abnormal sleep patterns. Breastfed infants, especially newborn or preterm infants, should be monitored for excessive sedation and adequate weight gain if this drug is used during lactation (LactMed, 2022). Discontinuation symptoms have been reported after stopping breastfeeding.

Briggs (2015) notes that venlafaxine provides a relatively high infant dose compared to other antidepressants and that long-term effects on neurobehaviour and cognitive development have not been adequately studied. If used, the infant should be monitored for short-term adverse effects. Schaefer (2015) concludes that venlafaxine is tolerable if compellingly indicated, but that whenever possible, drugs of choice among the tricyclic antidepressants or selective serotonin re-uptake inhibitors should be used in preference.

Side Effects

Abnormal ejaculation
Abnormal liver function tests
Agitation
Agranulocytosis
Akathisia
Alopecia
Anaphylaxis
Anorgasmia
Apathy
Aplastic anaemia
Asthenia
Blood dyscrasias
Bruxism
Chills
Confusion
Constipation
Convulsions
Decreased appetite
Delirium
Depersonalisation
Diarrhoea
Disturbances in accommodation
Dizziness
Dream abnormalities
Dry mouth
Dyskinesia
Dystonia
Ecchymosis
Erectile dysfunction
Erythema multiforme
Extrapyramidal effects
Gastro-intestinal haemorrhage
Glaucoma (closed angle)
Hallucinations
Headache
Hepatitis
Hot flushes
Hypertension
Hyponatraemia
Hypotension
Impaired co-ordination
Impaired urination
Inappropriate secretion of antidiuretic hormone
Increase in muscle tone
Increase in serum cholesterol (transient)
Increased prolactin
Insomnia
Mania
Menorrhagia
Menstrual disturbances
Metrorrhagia
Mucous membrane bleeding
Mydriasis
Myoclonus
Nausea
Nervousness
Neuroleptic malignant syndrome
Neutropenia
Night sweats
Orgasmic dysfunction
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Photosensitivity
Pollakiuria
Postural hypotension
Prolongation of QT interval
Prolonged bleeding
Pruritus
Psychomotor restlessness
Pulmonary eosinophilia
Rash
Reduced libido
Rhabdomyolysis
Sedation
Serotonin syndrome
Stevens-Johnson syndrome
Suicidal tendencies
Sweating
Syncope
Tachycardia
Tardive dyskinesia
Taste disturbances
Thrombocytopenia
Tinnitus
Torsades de pointes
Toxic epidermal necrolysis
Tremor
Urinary retention
Urticaria
Vasodilatation
Ventricular fibrillation
Ventricular tachycardia
Visual disturbances
Vomiting
Weight changes
Yawning

Effects on Laboratory Tests

Venlafaxine may affect immunoassay screening tests for phencyclidine (PCP) and amphetamine producing false-positive results. This can be expected for several days after discontinuing venlafaxine. Confirmatory tests such as gas chromatograph/mass spectrometry can be used to distinguish venlafaxine from PCP and amphetamine.

Withdrawal Symptoms and Signs

Discontinuation of venlafaxine commonly leads to withdrawal symptoms such as: dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation and anxiety, nausea and/or vomiting, tremor, vertigo, headache and flu syndrome.

When discontinuing venlafaxine, gradually reduce the dose over at least one to two weeks and monitor to minimise the risk of withdrawal reactions. The period required for discontinuation may depend on the dose, duration of therapy and the individual patient. In some patients, discontinuation may need to occur very gradually over periods of months or longer.

If intolerable symptoms occur resume previous prescribed dose. Subsequently, continue decreasing the dose at a more gradual rate.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: September 2022

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Venlafaxine 37.5mg/5ml Oral Solution. Rosemont Pharmaceuticals Limited. Revised July 2021.
Summary of Product Characteristics: Venlafaxine 75mg/5ml Oral Solution. Rosemont Pharmaceuticals Limited. Revised July 2021.

Summary of Product Characteristics: Venlafaxine 37.5mg tablets. Dexcel Pharma Ltd. Revised July 2021.
Summary of Product Characteristics: Venlafaxine 75mg tablets. Dexcel Pharma Ltd. Revised July 2021.

Summary of Product Characteristics: Venlafaxine 37.5mg tablets. Teva Pharma Ltd. Revised December 2021.
Summary of Product Characteristics: Venlafaxine 75mg tablets. Teva Pharma Ltd. Revised December 2021.

MHRA Drug Safety Update January 2021 Available at: https://www.mhra.gov.uk Last accessed: 11 February 2021

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 28 September 2022

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Venlafaxine. Last revised: 19 September 2022
Last accessed: 28 September 2022