Drugs List

Therapeutic Indications

Uses

Depressive illness

Contraindications

Children under 18 years
Within 2 weeks of discontinuing MAOIs
Breastfeeding

Precautions and Warnings

Electroconvulsive therapy
Patients over 65 years
Predisposition to haemorrhage
Predisposition to narrow angle glaucoma
Suicidal ideation
Hepatic cirrhosis
Hepatic impairment
History of coagulopathy
History of hypomania
History of mania
History of seizures
Pregnancy
Raised intra-ocular pressure
Renal impairment
Uncontrolled epileptic disorder

Patients at risk of suicide should be closely supervised
Advise patient ability to drive or operate machinery may be impaired
May reduce seizure threshold
Discontinue treatment if patient develops seizures
May cause hyponatraemia
Monitor patients for signs and symptoms of Neuroleptic Malignant Syndrome
Monitor patients for signs and symptoms of Serotonin Syndrome
Monitor patients for signs of aggression and agitation
Advise patients/carers to seek medical advice if changes in behaviour/mood
Advise patients/carers to seek medical advice if suicidal intent develops
Increased risk of fractures in patients over 50 years
May affect results of some laboratory tests
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue if patient enters a manic phase
Discontinue if serotonin syndrome develops
Discontinue immediately if hyponatraemia occurs
Reduce dose in elderly
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment

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 and adolescents, antidepressants may increase the risk of suicidal thoughts and self harm.

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.

Patients, (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal thoughts and behaviour, and to seek medical advice immediately if these symptoms present.

Rarely, the occurrence of serotonin syndrome has been reported in patients receiving SSRIs. A combination of symptoms, possibly including agitation, confusion, tremor, myoclonus and hyperthermia, may indicate the development of this condition. If serotonin syndrome occurs treatment with citalopram should be discontinued immediately and symptomatic treatment be initiated. If citalopram is used concomitantly with medicinal products with serotonergic effects such as sumatriptan or other triptans, tramadol and tryptophan, caution is advisable.

Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants; however, it has been reported more frequently with SSRIs than with other antidepressants. The CSM has advised that hyponatraemia should be considered in all patients who develop drowsiness, confusion or convulsions while taking an antidepressant.

In patients receiving SSRIs or TCAs, mainly those aged 50 years or older, a review of epidemiological studies showed an increased risk of bone fractures in these patients. The mechanism leading to this increased risk is unclear.

Mydriasis has been reported during treatment, having the potential to narrow the eye angle resulting in angle-closure glaucoma and increased intraocular pressure.

Pregnancy and Lactation

Pregnancy

Use vortioxetine with caution in pregnancy.

The manufacturers advises that vortioxetine must only be administered to pregnant women if the expected benefits outweigh any possible risk.

Epidemiological data suggest that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn. Although no studies have investigated an association of PPHN to SNRI treatment, this potential risk cannot be ruled out with vortioxetine taking into account the related mechanism of action (inhibition of the re-uptake of serotonin). Vortioxetine may also increase the risk of postpartum haemorrhage within the month prior to birth.

As with other serotonin reuptake inhibitors (SSRIs/SNRIs), discontinuation symptoms may occur in the newborns if the mother has used a SSRI/SNRI late in pregnancy: irritability, tremor, hypotonia, persistent crying, and difficulty in sucking or in sleeping. These symptoms may be due to either serotonergic effects or exposure symptoms. In the majority of cases, these complications are observed immediately or within 24 hours after partus.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Vortioxetine is contraindicated in breastfeeding.

It is expected that vortioxetine will be excreted into human milk and a risk to the suckling child cannot be excluded.

The manufacturer does not recommend concomitant vortioxetine and breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Aggression
Agitation
Angioedema
Constipation
Diarrhoea
Dizziness
Dream abnormalities
Flushing
General pruritus
Hyponatraemia
Insomnia
Mydriasis
Nausea
Night sweats
Pruritus
Serotonin syndrome
Sexual dysfunction
Urticaria
Vomiting

Presentation

Tablets containing vortioxetine

Drugs List

Therapeutic Indications

Uses

Depressive illness

Dosage

Adults

Elderly

Additional Dosage Information

Contraindications

Children under 18 years
Within 2 weeks of discontinuing MAOIs
Breastfeeding

Precautions and Warnings

Electroconvulsive therapy
Patients over 65 years
Predisposition to haemorrhage
Predisposition to narrow angle glaucoma
Suicidal ideation
Hepatic cirrhosis
Hepatic impairment
History of coagulopathy
History of hypomania
History of mania
History of seizures
Pregnancy
Raised intra-ocular pressure
Renal impairment
Uncontrolled epileptic disorder

Patients at risk of suicide should be closely supervised
Advise patient ability to drive or operate machinery may be impaired
May reduce seizure threshold
Discontinue treatment if patient develops seizures
May cause hyponatraemia
Monitor patients for signs and symptoms of Neuroleptic Malignant Syndrome
Monitor patients for signs and symptoms of Serotonin Syndrome
Monitor patients for signs of aggression and agitation
Advise patients/carers to seek medical advice if changes in behaviour/mood
Advise patients/carers to seek medical advice if suicidal intent develops
Increased risk of fractures in patients over 50 years
May affect results of some laboratory tests
Discontinue if patient develops neuroleptic malignant syndrome
Discontinue if patient enters a manic phase
Discontinue if serotonin syndrome develops
Discontinue immediately if hyponatraemia occurs
Reduce dose in elderly
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment

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 and adolescents, antidepressants may increase the risk of suicidal thoughts and self harm.

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.

Patients, (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal thoughts and behaviour, and to seek medical advice immediately if these symptoms present.

Rarely, the occurrence of serotonin syndrome has been reported in patients receiving SSRIs. A combination of symptoms, possibly including agitation, confusion, tremor, myoclonus and hyperthermia, may indicate the development of this condition. If serotonin syndrome occurs treatment with citalopram should be discontinued immediately and symptomatic treatment be initiated. If citalopram is used concomitantly with medicinal products with serotonergic effects such as sumatriptan or other triptans, tramadol and tryptophan, caution is advisable.

Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants; however, it has been reported more frequently with SSRIs than with other antidepressants. The CSM has advised that hyponatraemia should be considered in all patients who develop drowsiness, confusion or convulsions while taking an antidepressant.

In patients receiving SSRIs or TCAs, mainly those aged 50 years or older, a review of epidemiological studies showed an increased risk of bone fractures in these patients. The mechanism leading to this increased risk is unclear.

Mydriasis has been reported during treatment, having the potential to narrow the eye angle resulting in angle-closure glaucoma and increased intraocular pressure.

Pregnancy and Lactation

Pregnancy

Use vortioxetine with caution in pregnancy.

The manufacturers advises that vortioxetine must only be administered to pregnant women if the expected benefits outweigh any possible risk.

Epidemiological data suggest that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn. Although no studies have investigated an association of PPHN to SNRI treatment, this potential risk cannot be ruled out with vortioxetine taking into account the related mechanism of action (inhibition of the re-uptake of serotonin). Vortioxetine may also increase the risk of postpartum haemorrhage within the month prior to birth.

As with other serotonin reuptake inhibitors (SSRIs/SNRIs), discontinuation symptoms may occur in the newborns if the mother has used a SSRI/SNRI late in pregnancy: irritability, tremor, hypotonia, persistent crying, and difficulty in sucking or in sleeping. These symptoms may be due to either serotonergic effects or exposure symptoms. In the majority of cases, these complications are observed immediately or within 24 hours after partus.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Vortioxetine is contraindicated in breastfeeding.

It is expected that vortioxetine will be excreted into human milk and a risk to the suckling child cannot be excluded.

The manufacturer does not recommend concomitant vortioxetine and breastfeeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Aggression
Agitation
Angioedema
Constipation
Diarrhoea
Dizziness
Dream abnormalities
Flushing
General pruritus
Hyponatraemia
Insomnia
Mydriasis
Nausea
Night sweats
Pruritus
Serotonin syndrome
Sexual dysfunction
Urticaria
Vomiting

Effects on Laboratory Tests

False positive results have been reported for urine enzyme immunoassays for methadone during treatment. Caution should be taken when interpreting these results and if necessary confirmation via an alternative analytical technique should be considered.

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 2015

Reference Sources

Summary of Product Characteristics: Brintellix film coated tablets. Lundbeck Ltd. Revised July 2020.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 27 November 2020

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