Liothyronine for treatment resistant depression

Transcription

1 DERBYSHIRE JOINT AREA PRESCRIBING COMMITTEE (JAPC) SHARED CARE AGREEMENT FRAMEWORK Liothyronine for treatment resistant depression 1. REFERRAL CRITERIA Shared Care is only appropriate if it provides the optimum solution for the patient. Prescribing responsibility will only be transferred when it is agreed by the consultant and the patient s GP that the patient s condition is stable or predictable. Patients will only be referred to the GP once the GP has agreed in each individual case, subject to receiving the relevant clinical information. The patient will be given a supply of Liothyronine sufficient for 4 weeks maintenance therapy. 2. AREAS OF RESPONSIBILITY GP responsibilities 1. Reply to the request for shared care as soon as practicable. 2. Inform psychiatrist of any known contraindications or cautions to initiating liothyronine e.g. hypertension, angina, diabetes mellitus 3. Prescribe liothyronine (once daily in the morning for this indication) at dose indicated by psychiatrist 4. Follow psychiatrist advice on any changes in treatment. 5. Ensure that test results or monitoring parameters are in normal range before reauthorising repeat prescriptions (see monitoring parameters ). Do not increase dose of liothyronine without liaison with psychiatrist. 6. Monitor pulse and blood pressure regularly and copy aberrant readings to psychiatrist (see Monitoring ) 7. Monitor TFTs and/or perform regular clinical assessment to exclude signs of excessive dosage (see Monitoring below) if agreed with psychiatrist and copy reports to psychiatrist. 8. Monitor for cardiac changes and If new signs of cardiac dysfunction develop consult with psychiatrist to arrange ECG, giving due consideration to other potential causes. 9. Notify psychiatrist of any changes in patient s physical state e.g. significant new cardiac or bone morbidity. 10. Monitor for adverse effects and inform psychiatrist as appropriate. 11. Be alert to potential for drug interactions including serotonin syndrome if serotonergic agents are co-prescribed (see below). 12. If patient shows signs/symptoms of serotonin syndrome, consider urgent medical referral and stop liothyronine as a minimum and review the need to temporarily stop other co-prescribed serotonergic agents. 13. For patients on treatment for longer than 1 year and who also have above average risk of osteoporosis, follow local policy for Consultant responsibilities 1. Provide diagnosis and determine management strategy. 2. Contact GP to exclude contra-indications e.g. hypertension, angina; to check for cautions e.g. diabetes mellitus and for listing of concurrent medication. 3. Arrange for baseline testing (see Monitoring below) and copy results to GP. 4. Discuss benefits, side-effects and likely duration of treatment with patient with particular reference to possible short- or longterm side-effects and the need for regular checks of physical health e.g. blood tests, blood pressure, pulse (see below). 5. Inform patient that liothyronine is not licensed in this clinical indication and as such the effects may be less well understood compared to its use within licensed indication. Document this. 6. Provide advice re importance of checking that herbal, over the counter and new medicines are compatible with liothyronine. 7. Inform patient of symptoms of serotonin syndrome if liothyronine is to be combined with other serotonergic agents and the need to seek urgent medical advice if suggestive symptoms should arise. 8. Initiate treatment (usually once daily in morning for this indication) and titrate the dose where deemed appropriate, or advise GP of dose titration plan, being mindful of potential drug interactions. 9. If liothyronine is to be combined with other serotonergic agents, advise GP that patient has been informed of symptoms of serotonin syndrome and GP to be alert for need to stop liothyronine immediately should the syndrome be suspected, seek further advice and inform psychiatrist. 10. Advise GP on likely time course of treatment. 11. Ask the GP whether they are willing to participate in shared care and transfer prescribing on agreement, ensuring the patient has 4 weeks supply of liothyronine. 12. Agree with GP that they undertake the post-treatment TFTs and/or regular clinical assessment to exclude clinical signs of excessive dosage (e.g. diarrhoea see side-effects below). If the GP does not wish to monitor, undertake the monitoring and report/copy findings to GP. 13. Agree with GP that they undertake regular monitoring of pulse and blood pressure. 14. Agree with GP that they undertake post-treatment ECG if there is a risk of, or new signs of, cardiac dysfunction developing. If the GP does not wish to do this, undertake the monitoring and report/copy findings to GP (see Monitoring below). 15. Ensure relevant particulars of shared care framework are detailed within CPA documentation. 16. Monitor patient response (positive outcomes reported in studies lasting up to 8 weeks), assess for adverse effects and Page 1 of 7

2 bone densitometry monitoring and followup (see Monitoring ). 14. Discontinue treatment where psychiatrist s treatment review advises this. 15. Report any adverse effects to the referring specialist and the MHRA yellow card scheme. aim to review at least every 3 months initially. 17. If treatment is to continue for longer than 1 year, discuss with GP when evaluating risk against benefit (see below adverse effects long term use ). 18. Communicate promptly with the GP any changes in treatment. 19. Ensure clear arrangements for back up, advice, and support 20. Report any adverse effects to the MHRA yellow card scheme. Patient responsibilities To attend appointments and undergo the recommended monitoring. Share any concerns they have in relation to treatment with liothyronine, be aware of side effects and report any relevant symptoms promptly. Inform the psychiatrist or GP of any other medication being taken, including herbal or over-thecounter preparations. Seek advice before self-medicating with herbal or over-the-counter preparations. Report to the psychiatrist, GP or community psychiatric nurse if they do not have a clear understanding of their treatment. 3. COMMUNICATION AND SUPPORT i. Hospital contacts: ii. Out of hours contacts and procedures: Name: Derbyshire Healthcare Foundation Trust (DHCFT) Radbourne Unit Reception Telephone No: Fax No: Name: Hartington Unit Reception (DHCFT) Telephone No: Fax No: DHCFT Derby - Radbourne Unit Reception Open 24 hours contact as per i. DHCFT Chesterfield - contact via Chesterfield Royal Hospital Reception Telephone No: iii. Specialist support/resources available to GP including patient information: Summary of Product Characteristics, BNF 4. CLINICAL INFORMATION i. Prescribed indications Unlicensed use in euthyroid states as an adjunct to any antidepressant in managing unipolar treatment resistant depression (TRD). ii. Therapeutic summary Liothyronine is only licensed as a thyroid replacement hormone in thyroid disorders, especially in severe hypothyroid states where a rapid response is required. Whilst there are a handful of studies, albeit mostly carried out in unipolar, euthyroid, non-psychotic populations, which support the efficacy of liothyronine augmentation of tricyclic antidepressants, these are limited by having small sample sizes, mostly open-label design, being only partially controlled and looking at differing levels of treatment resistance. There are even fewer studies of liothyronine augmentation of SSRI antidepressants and the current generation of antidepressants. Further, it should be noted that most studies excluded patients who were suicidal, had a history of alcohol or substance misuse, or had medical conditions where liothyronine would be ill advised e.g. angina, arrhythmias. Bauer et al (3) concluded that lithium augmentation of antidepressants was the best documented augmentation strategy for managing TRD. The Sequenced Alternatives to Relieve Depression (STAR*D) study (4) found no statistical difference in efficacy between lithium or Liothyronine in SSRI augmentation but Liothyronine had superior tolerability. Until further compelling studies on the role of augmenting antidepressants with Liothyronine are published, Liothyronine augmentation is recommended to be positioned behind Lithium augmentation for managing TRD. However, Liothyronine provides an alternative approach with a different side-effect profile in a body of patients hitherto poorly responsive to the more evidence-based ways of managing TRD. Page 2 of 7

3 iii. Dose & Route of administration References: (1) BNF August 2015 (2) Derbyshire Joint Area Prescribing Committee Drug Assessment Liothyronine May 2008 (3) Bauer M, Adli M et al: Lithium augmentation therapy in refractory depression: clinical evidence and neurobiological mechanisms: Can J Psychiatry;2003;48; For use in augmenting response to an antidepressant, it need only be given once daily (in the morning), which reflects its mode of use in studies using liothyronine for this indication. Maintenance doses typically range from 20 to 50 microgram daily with a BNF maximum daily dose of 60 microgram. Smaller initial dose of 10 microgram is recommended in older adults. See also adverse effects below. 20microgram tablets are scored. iv. Liothyronine 20microgram is generally clinically equivalent to Levothyroxine 100microgram. Duration of treatment There is no recommended duration. Clinical efficacy should be assessed regularly on an individual basis and it is suggested that this be at least every 3 months. Studies reviewing response to Liothyronine augmentation have generally been between 2 and 8 weeks duration with STAR*D (4) lasting 12 weeks. Kelly and Lieberman (5) published on their case series of 17 patients, 14 of whom showed improvement with Liothyronine augmentation. Doses of Liothyronine up to 150 microgram daily were used and the average duration of treatment was 2 years (range ~1 to 7 years). Rosenthal et al. (6) suggest that Liothyronine may be considered an openended treatment option in patients with significant treatment resistance or a history of multiple episodes of MDD provided there is periodic review to exclude symptoms of hyperthyroidism or new cardiac disease. See also Adverse effects long term use below References: (4) Nierenberg AA, Fava M et al: Comparison of lithium and T3 augmentation following two failed medication treatments for depression; a STAR*D report. Am J Psychiatry 2006;163; (5) Kelly TF & Lieberman DZ: Long term augmentation with T3 in refractory major depression. J Affective Disorders; May 2009;115;1-2; (6) Rosenthal L, Whitney SG et al: T3 augmentation in major depressive disorder: safety considerations. Am J Psychiatry; Oct 2011; 168;10; (7) MHRA Drug Safety Update May 2013 vol 6, issue 10: S1 v. Adverse effects May include agitation, tremor, nervousness, sweating, palpitations, tachycardia, cardiac arrhythmias, anginal pain, serotonin syndrome (especially when combined with other serotonergic agents) and diarrhoea. After initiation, if metabolism increases too rapidly causing diarrhoea, rapid pulse or other adverse effects as listed above, reduce dose or withhold for 1-2 days and start again at a lower dose (1). Long term use There is suggestive evidence that prolonged use may predispose to bone demineralisation. Rosenthal et al (6) specifically reviewed safety of long term use of Liothyronine. They noted that subclinical hyperthyroidism has been associated with reduced bone mineral density and increased risk of osteoporosis especially in post-menopausal women and an increased risk Page 3 of 7

4 vi. vii. Monitoring Requirements Clinically relevant drug interactions of atrial arrhythmias. However, conversely, they refer to a study that found no significant difference in bone mineral density in pre- and postmenopausal women after at least 1 year of treatment with microgram Levothyroxine (not Liothyronine) daily (for bipolar disorder or major depressive disorder) and where TSH levels were maintained within normal range. Also Kelly and Lieberman (5) did not detect any skeletal or cardiac sequelae in their case series of 14 patients receiving long term treatment with Liothyronine. However it is worth bearing in mind that there is emerging evidence of a possible association between use of SSRI antidepressants and an increased fracture risk. Rosenthal et al (6) recommend that post-menopausal women on long term Liothyronine should be offered standard (calcium) and vitamin D supplementation and that bone densitometry be monitored every 2 years. Overdose Exaggeration of usual side-effects but may also include tachycardia, arrhythmias or convulsions for which treatment is symptomatic. ECG Baseline advised (and annual if cardiac risk). Avoid Liothyronine in cardiac disease (including hypertension, myocardial insufficiency or infarction). Monitor annually for patients with risk of cardiac dysfunction or if new signs of cardiac dysfunction develop (in particular, following a switch to a non-uk licensed product as bioequivalence cannot be assured (7). Review for evidence of ECG changes or arrhythmias. Blood pressure & Pulse rate Baseline. Review dosage/suitability of Liothyronine if hypertension or tachycardia present. Local recommendation to check 4 weeks after initiation or dose increase and then every 6 months or sooner if clinically indicated. Thyroid function including free T3, free T4 Baseline. During treatment either perform periodic TFTs or assess clinically only to rule out signs/symptoms of excessive dose e.g. palpitations, tremor. Whilst some brands without UK licence may not be bioequivalent, there is no identified therapeutic range in this unlicensed indication - efficacy is assessed based on clinical response. High risk osteoporosis e.g. post-menopause Only if used for longer than 1 year. Ensure adequate review, lifestyle advice; consider (calcium and) vitamin D supplementation. Re-evaluate risk and benefits of Liothyronine. If treatment continues, follow local policy regarding osteoporosis monitoring and follow-up. See BNF for full list of interactions. May enhance anticoagulant effect of Warfarin or other coumarins. May possibly raise Phenytoin serum level. Conversely, Phenytoin and barbiturates may enhance Liothyronine metabolism. Serotonergic syndrome Rare possibility especially in combination with other serotonergic agents (such as SSRIs, triptans used to treat migraine, certain opioid analgesics e.g. tramadol). The syndrome always features rapid onset within hours of either starting liothyronine (or other serotonergic agent) or of dose escalation. Mild symptoms such as akathisia, agitation, sweating, shivering, tremor may rapidly progress to more severe symptoms such as myoclonus, autonomic dysfunction, confusion and seizures. Stopping the serotonergic agent in the early stages usually brings about resolution within hours. Page 4 of 7

5 viii. Supply of ancillary Not applicable equipment ix. Supply, storage and Not applicable reconstitution instructions x. Prepared by Rachel Walsh, Senior Pharmacist Derbyshire Healthcare Foundation NHS Trust This does not replace the SPC, which should be read in conjunction with it. Date JAPC Agreed: December 2017 Review Date: November 2019 Page 5 of 7

6 Hospital No: «HOSPITAL_NUMBER» NHS No: «NHS_NUMBER» Sample Transfer Letter {Insert date} PRIVATE & CONFIDENTIAL «GP_TITLE» «GP_INITIALS» «GP_SURNAME» «GP_ADDRESS_1» «GP_ADDRESS_2» «GP_ADDRESS_3» «GP_ADDRESS_4» «GP_POSTCODE» DERBYSHIRE JAPC SHARED CARE AGREEMENT LETTER Dear «GP_TITLE» «GP_SURNAME» «FORENAME_1» «SURNAME» «DATE_OF_BIRTH» «CURRENT_ADDRESS_1» «CURRENT_ADDRESS_2» «CURRENT_ADDRESS_3» «CURRENT_ADDRESS_4» «CURRENT_POSTCODE» Your patient was seen on {Insert date} with a diagnosis of {Insert diagnosis}. I have initiated the following medication {Insert drug name} and am writing to ask you to participate in the shared care for this patient. This medication has been accepted as suitable for shared care by the Derbyshire Joint Area Prescribing Committee (JAPC). I agree to the secondary care responsibilities set out in the shared care agreement for this medication (available from I am therefore requesting your agreement to share the care of this patient. Where preliminary tests are set out in the agreement I have carried these out and results are below. Dose Regimen Date {Insert medicine name} started Date for GP to start prescribing {Insert medicine name} from The baseline test results are (if applicable): See overleaf for initiation criteria. I confirm I have explained to the patient: the risks and benefits of treatment, the baseline tests conducted, the need for monitoring, how monitoring will be arranged, and the roles of the consultant / nurse specialist, GP and the patient in shared care. I confirm the patient has understood and is satisfied with this shared care arrangement at this time. If you do NOT wish to participate in shared care for this patient, usually under clinical grounds, please complete the attached form. Yours sincerely {Consultant name} Page 6 of 7

7 GP RESPONSE TO SHARED CARE (only complete & send if NOT participating in shared care) Shared care is produced by GPs and specialists knowledgeable in the field of that drug usage. The shared care has been approved by the JAPC. This allows a more convenient service to the patient and cost effective use of NHS resources. Patient: Consultant: NHS No: Medicine requested for shared care: I will NOT be undertaking the GP responsibilities as described in the agreed shared care guideline. My clinical reasons for declining shared care for this patient are listed in the box below: Yours sincerely {GP name} {Surgery} Please send a copy of this response to: 1. The specialist/consultant requesting shared care 2. AN ANONYMISED COPY OF THIS FORM ONLY to the Medicines Management Clinical Effectiveness Team, 1st Floor East Point, Cardinal Square, 10 Nottingham Road, Derby, DE1 3QT or sderccg.derbyshiremedicinesmanagement@nhs.net (Sending a copy of this form to the Clinical Effectiveness Team will help to identify any inappropriate requests for shared care e.g. indication not covered, hospital monitoring requirements not fulfilled. It will also help to inform the CCG prescribing group of the reasons shared care is not being undertaken allowing for changes to be made in future updates to improve patient care). Page 7 of 7