APPENDIX 1 Shared Care Guideline Format s2

GREATER MANCHESTER INTERFACE PRESCRIBING GROUP

On behalf of the GREATER MANCHESTER MEDICINES MANAGEMENT GROUP SHARED CARE GUIDELINE for High Dose Venlafaxine i.e. Reference Number 300mg or > in severe depression VENL 09 fnl

Scope: Classification GMW Mental Health NHS FT, SHARED CARE GUIDELINE Bolton Primary Care Trust Salford Primary Care Trust, Trafford Primary care trust Issue date July 2008 Replaces Author(s)/Originator(s) GMW Mental Health NHS FT To be read in conjunction with the To be read in conjunction with SPC, NICE following documents GUIDANCE for Depression, Authorised by Authorised by Greater Manchester West Mental Health NHS Foundation Trust MMG Review Date July 2010 Approved by Interface Prescribing March 2009 Committee

1. Introduction

In line with NICE Guidance venlafaxine should be reserved for the treatment of depression in patients who have not responded to adequate trials of two antidepressants. These would normally be an SSRI followed by another SSRI or mirtazapine; alternatives include moclobemide, reboxetine, and lofepramine. Other tricyclics and venlafaxine may be considered, especially for more severe depression see SPC for more information on adverse effects and prescribing details. This shared care protocol covers situations where venlafaxine is prescribed for severe depression at doses greater than or equal to 300mg . Maximum dose 375mg daily. Venlafaxine at this dose is classed as amber by the Greater Manchester RAG Group. The initiation of doses of 300mg or above should only be undertaken with the advice or supervision of a specialist in Mental Health Services or a GP with Special Interest, with continuing supervision and monitoring of the patient.

2. Scope

Support of the use of this drug comes from NICE GUIDANCE www.nice.org.uk Depression: management of depression in primary and secondary care Clinical guideline 23(amended). SPC venlafaxine(Efexor) and BNF.

VENL 09 fnl 3. Clinical condition being treated

Licensed Indications: There are two preparations available; tablets 37.5mg, 75mg and capsules 75mg, 150mg known as XL. XL is licensed for major depressive disorder including depression with anxiety. It is also indicated for the prevention of relapses of the initial episode of depression or the prevention of the recurrence of new episodes. Moderate to severe Generalised Anxiety Disorder(GAD), moderate to severe generalised social anxiety disorder/social phobia. Tablets are licensed for the treatment of depressive disorder including depression accompanied by anxiety. Following an initial response the tablets are indicated for relapse prevention. Usual Dose for depression 75mg-225mg daily. Severely depressed patients or hospitalised patients max 375mg daily. Efexor XL i.e. slow release is licensed up to 225mg daily (pack sizes for 75mg, 150mg 14caps and 28caps) Efexor tablets are licensed up to 375mg daily. (pack sizes for 37.5mg,75mg 28tabs and 56tabs)

4. Product information and treatment regimen to be used

UPDATED VENLAFAXINE PRESCRIBING AND MONITORING ADVICE

Patients should have an adequate trial of 225mg of venlafaxine for at least 4 weeks before increasing the dose beyond 225mg.Initiation and treatment up to 225mg is classified as GREEN by the RAG.

Patients with increased risk factors for suicide should be carefully evaluated for the presence or worsening of suicide related behaviour and a limited amount of tablets should be provided to reduce the risk from overdose. A maximum of two weeks supply should be considered in these patients at initiation of treatment, during any dosage adjustment and until improvement occurs.

The initiation of or titration to doses of 300mg or above should only be undertaken with the advice or supervision of a specialist within Mental Health Services or a GP with Special Interest .The prescription of venlafaxine 300mg-375mg is classed as AMBER with shared care arrangements being in place with the continuing supervision and monitoring of the patient.

Venlafaxine should be used with caution in patients with established cardiac disease that may increase the risk of ventricular arrythmias e.g. recent MI.

Venlafaxine is contra-indicated in patients with an identified high risk of a serious cardiac ventricular arrhythmia (e.g. those with a significant left ventricular dysfunction, NYHA Class 111/1V) Venlafaxine remains contra- indicated in uncontrolled hypertension.

VENL 09 fnl The contra-indication for patients with an electrolyte imbalance and the requirement for a baseline ECG have been removed from product information.

Venlafaxine is not licensed for use and is not recommended in children and adolescents under the age of 18 with Major depressive disorder. Venlafaxine is contra-indicated in patients prescribed monoamineoxidase inhibitors.

Regular measurement of blood pressure is recommended for patients receiving venlafaxine. Dose related increases of BP have been reported commonly in patients on doses of > 200mg daily of venlafaxine. For patients who experience a sustained increase in blood pressure while receiving venlafaxine either dose reduction or discontinuation should be considered. However the patient’s overall physical health and mental health need to be taken into consideration and in particular whether the patient has had one episode or recurrent episodes of depression and the length of treatment course (see NICE Guidelines).For example patients with one severe episode but no symptoms of depression for a prolonged period may be considered for a dose reduction whereas a patient with multiple episodes who has failed a venlafaxine reduction in the past may be considered for antihypertensive therapy depending on their physical health and the size of the blood pressure increase. In all cases a risk/benefit discussion needs to take place with the patient, GP and Specialist to decide the safest option with regards to both Mental and Physical health. In patients where there has been a history of non- response to treatment, treatment with antihypertensive therapy could be considered.

5. Regimen Management

PROCEDURE FOR INITIATING SHARED CARE

 High dose venlafaxine may be initiated by the secondary care mental health specialist or the GP under supervision of a secondary care mental health specialist.  There should be an agreed care plan for monitoring the patient’s mental health ,physical health and side effects of drug treatment.  The GP should receive a copy of the care plan, venlafaxine SCP and completed referral form.(Appendix1) noting any recent BP readings. The GP should notify the psychiatrist ASAP and within 10days if they agree or not by signing the referral form.  The psychiatrist will ensure patient has adequate supplies of venlafaxine until shared care has been agreed.

VENL 09 fnl RESPONSIBILITIES OF THE PSYCHIATRIST

1. To establish the diagnosis and determine a management strategy and care plan in conjunction with the GP, other healthcare professionals and appropriate support agencies.

2. To initiate or recommend increasing the dose of venlafaxine to 300mg or greater.

3. To provide advice and agree an action plan if the GP reports poor response to treatment, signs of relapse, side effects or compliance problems.

4. To provide prescriptions until SCP has been agreed

5. To notify the GP of any relevant test results or changes to the care plan or prescription.

6. To discharge the patient to primary care when appropriate following agreement with the patient’s GP

RESPONSIBILITIES OF THE GENERAL PRACTITIONER

1. To refer patients with treatment-resistant depression. The GP may consider a trial of venlafaxine 75mg-225mg daily before referral or seeking advice.

2. To only prescribe 300mg-375mg daily after discussion and agreement with mental health services.

3. To prescribe 1-2weeks of medication at a time to patients at risk of overdosing.

4. To monitor BP at baseline and regularly especially at the beginning of treatment and after dose increases. If patients are prescribed more than 225mg daily 3monthly BP may be an appropriate frequency.

5. To notify mental health services of any relevant test results or changes to their drug treatment.

6. GP should seek advice from the psychiatrist or other agency where appropriate: a) deterioration in mental state or poor response b) difficult to manage side effects c) if patient has hypertension or develops heart disease d) if compliance is a problem e) advice on drug interactions when prescribing concomitant drugs

VENL 09 fnl 7. Once a decision to stop venlafaxine is made it should be withdrawn very gradually over at least 6-8weeks to avoid discontinuation symptoms if patient has taken it for 6-8months.After less than 8weeks withdraw over 1- 2 weeks. If a patient has been on long-term maintenance treatment reduce by 25% every 4-6weeks.

6. Summary of side-effects and interactions

SIDE EFFECTS

The most commonly observed adverse events associated with the use of venlafaxine in clinical trials, and which occurred more frequently than those which were associated with placebo were: nausea, insomnia, dry mouth, somnolence, dizziness, constipation, sweating, nervousness, asthenia and abnormal ejaculation/orgasm.

The occurrence of most of these adverse events was dose-related, and the majority of them decreased in intensity and frequency over time. They generally did not lead to cessation of treatment.

Adverse events observed with venlafaxine, from both spontaneous and clinical trials reports, are classified in body systems and listed below as very common (>1/10); common (<1/10 and >1/100); uncommon (<1/100 and >1/1000); rare (<1/1000); very rare (<1/10,000):

Blood and lymphatic system disorders - Uncommon: ecchymosis, mucous membrane bleeding; Rare: prolonged bleeding time, haemorrhage, thrombocytopenia; Very rare: blood dyscrasias (including agranulocytosis, aplastic anaemia, neutropenia and pancytopenia).

Cardiovascular and vascular disorders Common: hypertension, palpitation, vasodilatation; Uncommon: hypotension/postural hypotension, syncope, arrhythmias (including tachycardia); Very rare: Torsade de Pointes, QT prolongation, ventricular tachycardia, ventricular fibrillation.

Gastrointestinal disorders - Very common: constipation, nausea Common: anorexia, appetite decreased, diarrhoea, dyspepsia, vomiting; Uncommon: bruxism; Rare: gastrointestinal bleeding; Very rare: pancreatitis.

General disorders - Very common: asthenia, headache; Common: abdominal pain, chills, pyrexia; Rare: anaphylaxis

Metabolic and nutritional disorders - Common: serum cholesterol increased (particularly with prolonged administration and possibly with higher doses weight gain or loss; Uncommon: hyponatraemia including SIADH; Rare: hepatitis; Very rare: prolactin increased.

Musculo-skeletal disorders - Common: arthralgia, myalgia; Uncommon: muscle spasm; Very rare: rhabdomyolysis.

VENL 09 fnl Neurological disorders - Very common: dizziness, dry mouth, insomnia, nervousness, somnolence; Common: abnormal dreams, agitation, anxiety, confusion, hypertonia, paraesthesia, tremor; Uncommon: apathy, hallucinations, myoclonus; Rare: ataxia and disorders of balance and co- ordination, speech disorders including dysarthria, mania or hypomania, neuroleptic malignant syndrome-like effects, seizures serotonergic syndrome; Very rare: delirium, extrapyramidal disorders including dyskinesia and dystonia, tardive dyskinesia, psychomotor restlessness/akathisia.

Renal and urinary disorders - Common: urinary frequency; Uncommon: urinary retention.

Reproductive and breast disorders - Very common: anorgasmia, erectile dysfunction, abnormal ejaculation/orgasm; Common: decreased libido, impotence, menstrual cycle disorders; Uncommon: menorrhagia; Rare: galactorrhoea.

Respiratory system disorders - Common: dyspnoea, yawning; Very rare: pulmonary eosinophilia.

Skin and subcutaneous tissue disorders -Very common: sweating (including night sweats); Common: pruritus, rash; Uncommon: angioedema, maculopapular eruptions, urticaria, photosensitivity reactions, alopecia; Rare: erythema multiforme, Stevens Johnson syndrome.

Special senses - Common: abnormal vision/ accommodation, mydriasis, tinnitus; Uncommon: altered taste sensation.

INTERACTIONS

Potent CYP3A4 inhibitors e.g. ketoconazole ,erythromycin or drug combinations that inhibit both CYP3A4 and CYP2D6 should only be co- administered with venlafaxine when strictly indicated because of the possibility of clinically important interactions in patients with a ‘poor metaboliser’ phenotype. Specialist supervision is recommended for use of concomitant SSRIs.

7. Special considerations

TOXICITY IN OVERDOSAGE

Venlafaxine is involved in a higher rate of deaths from overdosage than the SSRIs but lower than the tricyclic antidepressants. Monitor high risk patients frequently and limit quantities - see section 4 for details. Overdoses of greater to or equal to 2g have been fatal although the majority of overdoses are non-fatal even at higher doses.

DISCONTINUATION REACTIONS

VENL 09 fnl Venlafaxine is associated with a greater frequency of withdrawal/discontinuation reactions than other antidepressants. The dose should be tapered gradually over a period of weeks according to the patient’s need. See under GP Responsibilities for guidance. The 37.5mg tablet can be broken in half to aid the slow reduction.

8. Back-up care available to GP from Hospital, including emergency contact procedures and help line numbers

9. Statement of agreement

Shared care is an agreement between the GP and the Consultant. This form is a request by the consultant to share the suggested care pathway of your patient. If you are unable to agree to the sharing of care and initiating the suggested medication, please make this known to the consultant within 14 days, ideally stating the nature of your concern.

10.Written information provided to the patient

11.Supporting References

SPC Efexor and EfexorXL

NICE Guidance Depression ; management of depression in primary and secondary care Clinical guideline 23(amended) April 2007

Wyeth Drug information

Antidepressant Discontinuation Syndromes Drug Safety 2001:24(3)183- 197

VENL 09 fnl APPENDIX 1 REFFERAL FORM FROM CONSULTANT PSYCHIATRIST TO GP

SHARED CARE PROTOCOL for VENLAFAXINE DOSES of 300mg or GREATER(HIGH DOSE) IN SEVERE DEPRESSION.

From (Name of Consultant Psychiatrist)______

To (Name of GP)______Name of GP practice or stamp______

Name of Patient______

Date of Birth______Hospital ID Number

Diagnosis______

Medication prescribed by Consultant Psychiatrist______

______Recent BP reading ______Date______

Name of Care co-ordinator/CPN______Tel No______

I would be grateful if we could adopt the shared care protocol for the above patient prescribed ‘high dose’ venlafaxine. I accept my responsibilities as outlined in the enclosed guideline.

Signed Consultant Psychiatrist______Date______

FOR the GP

I confirm I have received a copy of the patients Care Plan and SCP YES/NO I agree to share the care of the above patient prescribed ‘high dose’ venlafaxine. I accept my responsibilities as outlined in the enclosed guideline. YES/NO Signed GP______Date______

VENL 09 fnl