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Depression is a multi-faceted disorder6

Multiple pathways are thought to be responsible
for the different symptoms of depression9,10

Brintellix exhibits a multimodal pharmacological profile1

  • Brintellix is an antidepressant with a multimodal mechanism of action that combines modulation of 5-HT receptor activity with SERT inhibition11

Nonclinical data indicate that vortioxetine modulates neurotransmission in several systems, including predominantly the serotonin but probably also the norepinephrine, dopamine, histamine, acetylcholine, GABA and glutamate systems. However, the precise contribution of the individual targets to the observed pharmacodynamic profile remains unclear and caution should be applied when extrapolating animal data directly to man.1

5-HT, 5-hydroxytryptamine receptors or serotonin receptors; SERT, serotonin transporter

Brintellix may help give your patients diagnosed with major depressive disorder (MDD) the life they deserve.2,3,5

Find out more about Brintellix efficacy in the Patient experience section

Patient experience

NICE and SMC Guidelines and recommendations

National Institute for Health and Care Excellence (NICE)*12

  • Brintellix is recommended by NICE Technology Appraisal Guidance [TA367] as an option for treating major depressive episodes in adults whose condition has responded inadequately to two antidepressants within the current episode*12
  • People whose treatment with Brintellix is not recommended in this NICE guidance, but was started within the NHS before this guidance was published, should be able to continue treatment until they and their NHS clinician consider it appropriate to stop12

Scottish Medicines Consortium (SMC)13

  • The SMC has accepted Brintellix for restricted use in the treatment of major depressive episodes in adults who have experienced an inadequate response** to two or more previous antidepressants13
*NICE guidance is also valid in Wales - When a NICE technology appraisal recommends the use of a drug or
treatment, or other technology, the NHS in Wales must usually provide funding and resources for it within 3 months of the guidance being published.12,14 **Either due to lack of adequate efficacy and/or safety concerns/intolerability13

Brintellix: a generally well-tolerated option for your adult patients diagnosed with MDD1,15,16

Brintellix exhibits a low withdrawal rate due to tolerability issues in short-term studies vs. placebo15

Findings based on an analysis designed to assess the tolerability and safety of Brintellix in 11 randomised, double-blind, placebo-controlled short-term studies in depression and five long-term studies15

Nausea with Brintellix is usually mild to moderate and transient1,15

The most common adverse reaction with Brintellix is nausea. Nausea with Brintellix is usually mild to moderate, transient, and does not generally lead to treatment discontinuation1,15 Gastrointestinal adverse reactions, such as nausea, occurred more frequently in women than men.1

Brintellix showed no clinically meaningful effects on hepatic, renal, and cardiac function1,15,17

Minimal effects on body weight relative to placebo1,15

Brintellix is associated with a mean weight increase of <1 kg in patients treated with Brintellix for up to 12 months 1,15 From an analysis designed to assess the tolerability and safety of Brintellix in 11 randomised, double-blind, placebo-controlled short-term studies in depression and five long-term studies. 10 of the short-term studies included participants aged 18-75, and one included participants aged over 651

Low rate of patient-reported sexual dysfunction at 5-15 mg*1,15

Patient-reported sexual dysfunction with Brintellix was low, and similar to that in the placebo group during short-and long-term treatment (1.6-1.8% vs 1.0%)15 *Brintellix 15 mg is not available for use in the UK. The 20 mg dose of Brintellix was associated with an increase in sexual dysfunction compared to placebo.1 There have been reports of sexual dysfunction with doses below 20 mg during the post-marketing period.1 Sexual dysfunction was assessed using the Arizona Sexual Experience Scale (ASEX)1

Brintellix does not increase the incidence of insomnia or somnolence relative to placebo†1,15

†In a pooled analysis of 11 short-term (6/8 week) randomised, double-blind, placebo-controlled clinical trials, Brintellix did not increase the incidence of insomnia or somnolence relative to placebo.1,15 There have been reports of insomnia during the post-marketing period1
For full details please refer to the Brintellix Summary of Product Characteristics1
MDD, major depressive disorder.

Brintellix Dosing: Prescribing Brintellix for your patients

Brintellix Dosing:1

  • The starting and recommended dose for adult patients < 65 years is Brintellix 10 mg once daily
  • Can be increased or decreased between 5 mg and 20 mg daily, depending on the individual patient‘s response
  • After the depressive symptoms resolve, treatment for at least 6 months is recommended for consolidation of the antidepressive response

Elderly patients:1

  • Patients aged ≥65 should always start on 5 mg once daily
  • Caution is advised when treating patients ≥65 years old with doses higher than 10 mg once daily for which data are limited

Renal or hepatic impairment:1

  • No dose adjustment is needed based on renal or hepatic function

Treatment discontinuation:1

  • In the clinical studies there was no clinically relevant difference to placebo in the incidence or nature of the discontinuation symptoms after treatment with Brintellix
  • Cases describing discontinuation symptoms have been reported in the post-marketing setting
  • Discontinuation symptoms have included dizziness, headache, sensory disturbances (including paraesthesia, electric shock sensations), sleep disturbances (including insomnia), nausea and/or vomiting, anxiety, irritability, agitation, fatigue and tremor
  • These symptoms may occur within the first week of Brintellix discontinuation
  • A gradual reduction in dosage may be considered to avoid the occurrence of discontinuation symptoms. However, there is insufficient data to provide specific recommendations for a tapering schedule for patients treated with Brintellix
For full details please refer to the Brintellix Summary of Product Characteristics1
Taking Brintellix:1
  • Can be taken with or without food at any time of the day

Brintellix contraindications and drug interactions1

Key considerations when combining Brintellix with other medications:1

Contraindications1
  • Hypersensitivity to active substance or excipients (please refer to the Summary of Product Characteristics for full list of excipients)
  • Concomitant use with non-selective monoamine oxidase inhibitors (MAOIs) or selective monoamine oxidase-A (MAO-A) inhibitors (moclobemide)
Monitor for serotonin syndrome:1
  • Irreversible selective monoamine oxidase-B (MAO-B) inhibitors (rasagiline, selegiline) –administer with caution
  • Drugs with a serotonergic effect (opioids (including tramadol); triptans (including sumatriptan)
  • St John’s wort — concomitant use of antidepressants with serotonergic effect and St. John’s wort (Hypericum perforatum) may result in a higher incidence of adverse reactions including serotonin syndrome
Proceed with caution:1
  • Medicinal products lowering the seizure threshold [e.g. antidepressants (tricyclics, SSRIs, SNRIs), neuroleptics (phenothiazines, thioxanthenes and butyrophenones), mefloquine, bupropion, tramadol]
  • ECT (electroconvulsive therapy)
  • CYP2D6 inhibitors (bupropion, quinidine, fluoxetine, paroxetine) – consider a dose adjustment
  • Broad CYP450 inducers (rifampicin, carbamazepine, phenytoin) – consider a dose adjustment
  • Anticoagulants and medicinal products known to affect platelet function
No known effects with:1
  • Diazepam
  • Oral contraceptives

Given that subjects with renal or hepatic impairment are vulnerable and given that the data on the use of Brintellix in these subpopulations are limited, caution should be exercised when treating these patients.

Brintellix: Practical guidance on switching1,18

Switching to Brintellix from other antidepressants:18

SSRIs and SNRIs18
  • Direct switch possible
Mirtazapine18
  • Cross taper cautiously (usually over 1 to 2 weeks)
Tricyclic antidepressants (TCAs)18
  • Halve TCA dose, add Brintellix and then withdraw the TCA slowly
Monoamine oxidase inhibitors (MAOIs)18
  • Taper and stop MAOI
  • Wait 14 days before initiating Brintellix
  • Guidance based on general recommendations from switching between classes in the Maudsley Prescribing Guidelines on Psychiatry.18 These are third party recommendations and prescribers should use them in conjunction with their own clinical judgement.
  • The advice given should be treated with caution and patients should be very carefully monitored when ‘switching’ as stated in the Maudsley Guidelines.18
  • It is very important that prescribers consult the Summary of Product Characteristics for any medication they are considering switching from prior to making the switch.
  • MAOI, monoamine oxidase inhibitor; MAO-A, monoamine oxidase A; MAO-B, monamine oxidase B; SNRI, serotonin-noradrenaline reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.

Brintellix special warnings and precautions1

Use in paediatric population1

  • Brintellix is not recommended for the treatment of depression in children aged 7 to 11 years since the safety and efficacy of Brintellix have not been established in this age group. Brintellix should not be used in adolescents aged 12 to 17 years with major depressive disorder (MDD) because efficacy has not been demonstrated (see section 5.1 of SmPC). In general, the adverse reaction profile of Brintellix in adolescents was similar to that seen for adults except for higher incidences reported in adolescents than in adults for abdominal pain-related events and suicidal ideation (see section 4.8 and 5.1 of SmPC). In clinical studies in children and adolescents treated with antidepressants, suicide-related behaviour (suicide attempt and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour, anger) were more frequently observed than in those treated with placebo.

Suicide/suicidal thoughts or clinical worsening1

  • 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 suicide may increase in the early stages of recovery.
  • Patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical studies of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo, in patients less than 25 years old.
  • Close supervision of patients and in particular those at high risk should accompany treatment especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted to the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Seizures1

  • Seizures are a potential risk with antidepressants. Therefore, Brintellix should be introduced cautiously in patients who have a history of seizures or in patients with unstable epilepsy (see section 4.5 of SmPC). Treatment should be discontinued in any patient who develops seizures or for whom there is an increase in seizure frequency.

Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS)1

  • Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS), potentially life-threatening conditions, may occur with Brintellix. The risk of SS or NMS is increased with concomitant use of serotonergic-active substances (including opioids and triptans), medicinal products that impair the metabolism of serotonin (including MAOIs), antipsychotics, and other dopamine antagonists. Patients should be monitored for the emergence of signs and symptoms of SS or NMS (see sections 4.3 and 4.5). of SmPC).
  • Serotonin Syndrome symptoms include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, uncoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea). If this occurs, treatment with Brintellix should be discontinued immediately and symptomatic treatment should be initiated.

Mania/hypomania1

  • Brintellix should be used with caution in patients with a history of mania/hypomania and should be discontinued in any patient entering a manic phase.

Aggression/agitation1

  • Patients treated with antidepressants, including Brintellix, may also experience feelings of aggression, anger, agitation and irritability. Patient’s condition and disease status should be closely monitored. Patients (and caregivers of patients) should be alerted to seek medical advice, if aggressive/agitated behaviour emerges or aggravates.

Haemorrhage1

  • Bleeding abnormalities, such as ecchymoses, purpura and other haemorrhagic events, such as gastrointestinal or gynaecological bleeding, have been reported rarely with the use of antidepressants with serotonergic effect, including Brintellix. SSRIs/SNRIs may increase the risk of postpartum haemorrhage, and this risk could potentially apply also to Brintellix (see section 4.6 of SmPC). Caution is advised in patients taking anticoagulants and/or medicinal products known to affect platelet function [e.g., atypical antipsychotics and phenothiazines, most tricyclic antidepressants, non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA)] (see section 4.5 of SmPC) and in patients with known bleeding tendencies/disorders.

Hyponatraemia1

  • Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported rarely with the use of antidepressants with serotonergic effect (SSRIs, SNRIs). Caution should be exercised in patients at risk, such as the elderly, patients with cirrhosis of the liver or patients concomitantly treated with medicinal products known to cause hyponatraemia. Discontinuation of Brintellix should be considered in patients with symptomatic hyponatraemia and appropriate medical intervention should be instituted.

Glaucoma1

  • Mydriasis has been reported in association with use of antidepressants, including Brintellix. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure and angle-closure glaucoma. Caution is advised when prescribing Brintellix to patients with increased intraocular pressure, or those at risk of acute narrow-angle glaucoma.

Elderly1

  • Data on the use of Brintellix in elderly patients with major depressive episodes are limited. Therefore, caution should be exercised when treating patients ≥ 65 years of age with doses higher than 10 mg Brintellix once daily (see sections 4.2, 4.8 and 5.2 of SmPC).

Renal or hepatic impairment1

  • Given that subjects with renal or hepatic impairment are vulnerable and given that the data on the use of Brintellix in these subpopulations are limited, caution should be exercised when treating these patients. (See section 4.2 and 5.2 of SmPC).

Brintellix has a low rate of treatment-emergent adverse events1,15

The most common adverse reaction with Brintellix was nausea (very common (≥1/10)1

Other common adverse events (≥1/100 to < 1/10) included:1

  • Abnormal dreams
  • Dizziness
  • Diarrhoea, constipation, vomiting
  • Pruritus, including pruritus generalised, hyperhidrosis

Please refer to the Summary of Product Characteristics for a full list of adverse reactions (based on information from clinical trials and post-marketing experience)1

In a pooled analysis of 11 short-term (6/8 week) randomised, double-blind, placebo-controlled clinical trials:15

Treatment-emergent adverse events (TEAEs) of ≥5% incidence in any treatment group15

Preferred term Placebo (n=1817) Brintellix 5 mg (n=1013) Brintellix 10 mg (n=894) Brintellix 15 mg (n=449) Brintellix 20 mg (n=662) Venlafaxine 225 mg (n=113) Duloxetine 60 mg (n=753)
% patients with TEAEs 58 65 61 69 65 75 76
Nausea 8 21 23 31 28 34 34
Headache 13 14 13 15 13 28 13
Dry mouth 6 7 6 6 7 17 17
Dizziness 6 6 5 7 6 10 12
Diarrhoea 5 7 6 9 6 4 9
Vomiting 1 3 4 7 5 4 4
Insomnia 4 5 4 2 3 16 8
Constipation 3 3 4 6 4 10 10
Somnolence 2 3 3 3 3 1 9
Fatigue 3 3 3 4 2 10 8
Decreased appetite 1 2 1 1 2 1 7
Sexual dysfunction 1 2 2 2 2 12 5
Hyperhidrosis 2 2 2 2 1 15 7

Duloxetine and venlafaxine were included as active references for study validation only15

TEAEs above the orange line occur with a frequency ≥5% for Brintellix15

Brintellix 15 mg is not available for use in the UK.

Adverse events should be reported.

Reporting forms and information can be found at http://www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Adverse events should also be reported to Lundbeck Limited, Medical Information, on: 01908 638972 or Email: SafetyLuUnitedKingdom@lundbeck.com

References
  • Lundbeck. Brintellix. Summary of Product Characteristics GB and NI.
  • Chokka P et al. CNS Spectrums. 2019 Dec;24(6):616-27.
  • Cao B et al. Frontiers in psychiatry. 2019 Jan 31;10:17.
  • Baune BT et al. Int J Neuropsychopharm. 2018 Feb;21(2):97-107.
  • Fagiolini A et al. J Affect Disord. 2021 Mar 15;283:472-9.
  • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition, Text Revision (DSM-5-TR). 2022. American Psychiatric Association Publishing. https://doi.org/10.1176/appi.books.9780890425787 [Last accessed September 2023].
  • NHS. Symptoms – clinical depression. Available at: www.nhs.uk/mental-health/conditions/clinical-depression/symptoms/ [Last (accessed) September 2023].
  • Marazziti D et al. Eur J Pharmacol 2010 Jul;626(1):83–86.
  • Saltiel PF, Silvershein DI. Neuropsychiatr Dis Treat. 2015 Mar 31;11:875-888.
  • Nutt DJ. J Clin psychiatry. 2008 Jan 1;69(Suppl E1):4-7.
  • Sanchez C et al. Pharmacology & therapeutics. 2015 Jan 1;145:43-57.
  • National Institute For Health And Care Excellence. TA367. November 2015.
  • Scottish Medicines Consortium. SMC No. (1158/16). July 2016.
  • All Wales Medicines Strategy Group. 1199 SOA. April 2014.
  • Baldwin DS et al. J Psychopharmacol 2016;30:242–252.
  • Citrome L. J Affect Disord 2016;196:225–233.
  • Wang Y et al. Clin Pharmacol Drug Dev 2013;2:298–309.
  • The Maudsley prescribing guidelines in psychiatry. 14th ed. Wiley Blackwell, 2021;335–341.
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