Dorset Medicines Advisory Group SHARED CARE GUIDELINES FOR THE USE OF MONOAMINE OXIDASE INHIBITORS (MAOIs) – PHENELZINE and ISOCARBOXAZID INDICATION Monoamine Oxidase Inhibitors (MAOIs) are licensed for the treatment of depressive illness especially where other trials of antidepressants have failed. This shared care guideline recommends that MAOIs are initiated under specialist supervision due to their tolerability, significant dietary and pharmacological interactions. Once a patient’s condition has stabilised, it should be considered the MAOI can be prescribed by the patients GP under this shared care agreement. NICE CG90 Depression in Adults: recognition and management recommends that when reviewing drug treatment for a person with depression whose symptoms have not adequately responded to initial pharmacological interventions: • check adherence to, and side effects from, initial treatment, increase the frequency of appointments using outcome monitoring with a validated outcome measure, • be aware that using a single antidepressant rather than combination medication or augmentation is usually associated with a lower side-effect burden, • consider reintroducing previous treatments that have been inadequately delivered or adhered to, including increasing the dose, • consider switching to an alternative antidepressant. When switching to another antidepressant consider switching to: o initially a different SSRI or a better tolerated newer-generation antidepressant, o subsequently, an antidepressant of a different pharmacological class that may be less well tolerated, for example venlafaxine, a tricyclic antidepressant or an Monoamine-oxidase inhibitor. Due to the a more favourable side effect profile, less interactions and acquisition costs, phenelzine should be considered the first line MAOI of choice. AREAS OF RESPONSIBILITY FOR SHARED CARE This shared care agreement outlines suggested ways in which the responsibilities for managing the prescribing of MAOIs can be shared between the specialist setting and the patient’s GP (if different). GPs are invited to participate. If the GP is not confident to undertake these roles, then he or she is under no obligation to do so. In such an event, the total clinical responsibility for the patient for the diagnosed condition remains with the specialist. If a specialist asks the GP to prescribe this drug, the GP should reply to this request as soon as practicable. Sharing of care assumes communication. The intention to share care is usually explained to the patient by the doctor initiating treatment. It is important that patients are consulted about treatment and are in agreement with it. The doctor who prescribes the medication legally assumes clinical responsibility for the drug and the consequences of its use. REFERRAL AND INITIATION Monoamine oxidase inhibitors should only be initiated under specialist supervision. Phenelzine should be considered first line MAOI of choice. 1 Dorset Medicines Advisory Group Specialist Responsibilities 1 Prescribing until maintenance regime established. 2 Discussion of risks and benefits with patients and carers in particular the dietary restrictions and interactions with medication, including OTC. Specialist Responsibilities 3 Provision of written information on use, side effects and dietary restrictions 4 Provide details of concurrent medication prescribed via psychiatric secondary care to GP. 5 Provide details of patient follow up including care plan. 6 Inform GP of any identified problems e.g. compliance with treatment. 7 Provide details of mental health key worker if appropriate. 8 Provide details of concurrent medication prescribed via psychiatric secondary care to GP. 9 Provide support to GP in response to queries about switching antidepressants General Practitioner Responsibilities 1 Provide details of any concurrent medication, coexisting health problems and compliance issues to the specialist 2 Continued discussion of risks and benefits of medication with patients and carers as required. 3 Prescribing once maintenance doses established. Switching or discontinuation should only be done through the specialist 4 Continued monitoring as agreed with secondary care and referral back to secondary care if patient becomes non-compliant and/or if mental state 5 Continued discussion of risks and benefits of medication with patients and carers as required. 6 Prescribing once maintenance doses established. Switching or discontinuation should only be done through the specialist deteriorates 7 Respond to adverse reactions and advise on concomitant medication. 8 Update specialist on any changes in medical condition or prescribed concomitant medication until discharged from specialist services 9 Seek support from specialist when considering switching antidepressants Patient's role (or that of carer) 1 Take medication as prescribed 2 Follow instructions re diet 3 Report any side effects 4 Report worsening of depressive symptoms 2 Dorset Medicines Advisory Group SUPPORTING INFORMATION Monitoring Regular blood pressure measurement is recommended during initiation and routine checks should be made during maintenance. 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. Dosage and Administration Tranylcypramine Initially 10mg twice daily not later than 3pm, increasing the 2nd dose to 20mg after 1 week if necessary. Doses above 30mg daily under close supervision only; usual maintenance dose 10mg daily. Elderly (over 65 years) Use with great caution and at reduced dose. Children Not recommended. Refer to manufacturer‘s advice on concurrent electroconvulsive therapy and doses. Phenelzine One 15mg tablet three times a day. A response is usually seen within the first week. If no response is evident after two weeks, the dosage may be increased to a maximum of one 15mg tablet four times a day. Doses of up to two 15mg tablets three times a day may be used in hospitals. The effectiveness of the drug may not become apparent in less than 4 weeks therapy. After a satisfactory response has been achieved, the dosage may be reduced very gradually to a suitable maintenance level. This may be as low as one 15mg tablet every other day. Elderly (over 65 years): As for adults. Isocarboxazid A daily dose of 30mg, in single or divided doses, should be given until improvement is obtained. The maximal effect is only observed after a period varying from 1 - 4 weeks. If no improvement has been seen by 4 weeks, doses up to 60mg may be tried, according to the patient's tolerance, for no longer than 4 - 6 weeks, provided the patient is closely monitored because of the increased risk of adverse reactions occurring. Once the optimal effect is achieved, the dose should be reduced to the lowest possible amount sufficient to maintain the improvement. Clinical experience has shown this to be usually 10 - 20mg daily but up to 40mg daily may be required in some cases. The elderly The elderly are more likely to experience adverse reactions such as agitation, confusion and postural hypotension. Half the normal maintenance dose may be sufficient to produce a satisfactory clinical response. 3 Dorset Medicines Advisory Group Duration of treatment NICE guidance recommends that people with depression who benefit from treatment with antidepressants are advised to continue with treatment for at least 6 months after remission, extending to at least 2 years for people at risk of relapse. Contraindications Common to all MAOIs Cerebrovascular disease, severe cardiovascular disease, actual or suspected phaeochromocytoma, liver impairment, blood dyscrasias, hyperthyroidism. MAOIs are not indicated in manic phase. Selective serotonin reuptake inhibitors (SSRIs): Cases of serious and sometimes fatal reactions (serotonin syndrome) have been reported in patients receiving monoamine oxidase inhibitors (MAOIs) in combination with SSRIs, and in patients who have recently discontinued an SSRI and have been started on a MAOI. Treatment with SSRIs should only be started 2 weeks after discontinuation of Isocarboxazid. Conversely, treatment with tranylcypromine should not be started until at least a week after stopping a SSRI or related anti-depressant (at least 5 weeks for fluoxetine). Use of MAOIs with or after fluvoxamine has been reported to produce a serotonin syndrome, sometimes fatal. Avoid use with other MAOIs, as symptoms of overdose are possible; or with buspirone, since increased blood pressure may occur. Due to risk of hypertensive crisis or severe convulsive seizures avoid for at least 2 weeks after stopping previous MAOI (for e.g. furazolidone, isocarboxazid, pargyline HCl and procarbazine HCl) and then start at a reduced dose. Similarly, at least a week should elapse between the discontinuance of tranylcypromine and the administration of another MAOI, or the re- administration of tranylcypromine. Tranylcypromine. Reports of hyperactivity, hypertonicity, hyperpyrexia, coma and death have been associated with the use of tranylcypromine in combination with tricyclic antidepressants; Tetracyclic antidepressants should also be avoided. The use of clomipramine in patients already on tranylcypromine may be particularly hazardous. Phenelzine should