Antidepressant Treatment of Depression

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Bryce Campbell
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1 Antidepressant Treatment of Depression PLEASE REFER TO INTEGRATED CARE PATHWAY FOR INFORMATION RELATING TO THE OVERALL MANAGEMENT OF DEPRESSION SSRI s are first choice agents because they are as effective as TCA s but less likely to be discontinued because of side-effects (NICE CG90). Final choice will depend on patient characteristics; co-morbidity, suicide risk (drug toxicity in overdose), patient choice and potential for drug interactions. Use lowest effective dose and monitor carefully at the start of treatment or when there is a dose change for signs of agitation or other adverse effects. Younger patients are more susceptible to these effects and should be monitored weekly initially. Avoid administering two antidepressants together unless under specialist guidance. Where patients are taking two antidepressants for two different indications (e.g. depression and pain), consider rationalising this to a single agent. For information regarding switching of antidepressants see Appendix. NB: Escitalopram is NOT recommended for use in NHS Dumfries and Galloway First Line Preferred Choice In recurrence of previously treated depression first choice is previously effective antidepressant. Fluoxetine 20mg od ( 0.93/28 Effective, safe and inexpensive; good for patients with anergia / psychomotor retardation, long half-life so better where compliance is problematic. Can worsen insomnia (prescribe in morning) and agitation. Sertraline 50mg od ( 4.17/28 ) Should be considered if it is important to minimise the effect on the QT interval or post MI. After 4 : No improvement consider switch to alternative antidepressant (and see comment below). Partial improvement continue same dose and reassess at 2 4 (BAP 2008) There is a risk of GI bleeding with SSRIs use with caution in patients over 80 years, with prior GI bleed or with those on aspirin or NSAIDs (consider co-prescription of PPI). Second Line Consider dose increase only if partial response with minimal side effects. SSRIs demonstrate a relatively flat dose response curve If first choice SSRI is ineffective or poorly tolerated it is reasonable to try another SSRI Mirtazapine 30mg at night ( 1.75/28) Less nausea, headache or sexual dysfunction than other SSRIs. May have faster onset. Has anxiolytic action. Sedation and weight gain maybe problematic at lower doses. Third Line Venlafaxine: mg daily as standard release tablets in 2 divided doses. Contraindicated in patients with identified very high risk of a serious cardiac ventricular arrhythmia (e.g. those with a significant left ventricular dysfunction, NYHA Class III/IV) or uncontrolled hypertension. Dose related increase in blood pressure - regular measurement of blood pressure is recommended, especially over 150mg daily. Doserelated QTc prolongation. Please note at less than 150mg daily Venlafaxine is an expensive SSRI. Duloxetine 60mg OD ( /28 ) Incidences of associated hypertension, palpitations and tachycardia have been reported Trazodone 150mg daily ( 4.10 /28 ) useful in concomitant anxiety / insomnia Lofepramine 70mg bd ( 15.99/28) Less cardiotoxic than other tricyclics in overdose, also less sedating and anticholinergic side-effects. Early LFT elevation usually transient. Paroxetine 20mg ( 2.07 /28 ) Consultant Initiated Only MAOIs require specialist expertise to prescribe safely. Indicated for major depression. Take after food. Food restrictions apply to avoid tyramine overload and subsequent hypertensive crisis. Avoid sympathomimetics. Washout period required see switching guide attached. Combination antidepressants Treatment or augmentation with a mood stabiliser e.g. Lithium, anticonvulsant or antipsychotic. Agomelatine NOT SMC approved, via Exceptional Use Committee approval only NB This group of drugs should only be initiated on the recommendation of a Consultant for treatment of depression. If these drugs are to be prescribed there needs to be a clear reason documented. Quetiapine for treatment of depression is NOT SMC approved, via Exceptional Use Committee approval only See BNF for licensed dosage range for the above drugs Department of Psychiatry & Prescribing Support Team: March

2 If no response to first drug after 4 (6 in elderly) 1. Reconsider diagnosis 2. Check compliance at prescribed dose 3. Consider increase in dose in line with product license 4. Consider switching to another antidepressant (see table above for drug choices and guide below for information on switching drugs). 5. If partial response is shown, continue for another two and re-assess 6. Consider smoking status as some antidepressants (e.g. Tricyclics, Duloxetine, Agomelatine, Fluvoxamine, Mirtazapine) may need higher doses in smokers. See D&G Prescribing Support Website Smoking cessation guidance If no/poor response is achieved to the second agent after ensuring the above 1. Refer patient to CMHT 2. Or If GP with specialist interest in depression: treat with third line agent. For more information on third line options see NICE guidance on treatment resistant depression. St John s Wort. This is a popular OTC herbal treatment used for mild to moderate depression with limited trial evidence of efficacy. Quality and response to different brands can be variable and unpredictable. Patients may experience a withdrawal syndrome on stopping abruptly after approximately 8 treatment. Interacts with anti-epileptics, ciclosporin, digoxin, oral contraceptives, theophylline and warfarin. See BNF for others. Avoid combination with other antidepressant agents. Patient Education - Medication Antidepressants are not addictive, nor do you become tolerant to them. (Attempt to dispel stigma) They take 2-4 to work properly. Take the tablets every day and do not stop suddenly unless advised. If symptoms are not resolving the dose or type of antidepressant might have to be changed You will need to take antidepressant for at least 6 months after you feel better. should be done gradually so discuss with GP first. Many side-effects are short-term and disappear after a couple of if you keep taking your antidepressant Avoid taking alcohol, especially early in treatment, as it is a depressant. Have realistic expectations, you will still have bad and set backs. Useful Web addresses: Royal College of Psychiatry (variety of peer reviewed patient information leaflets on mental health issues) SIGN guidelines Medicine data sheets Moodjuice self help resource NICE Guidelines Life skills resource D & G Prescribing Website Driving Advise patients to avoid driving or operating machinery if they are affected by drowsiness, particularly during the first month of treatment. The DVLA recommends avoiding drugs that have antimuscarinic effects. In cases where suicidality, risk to the public, or psychosis is present, the DVLA should be informed by the patient. The DVLA usually require driving to cease until a period of 3 months from remission. See for more details Pregnancy Use non-drug treatment where possible and appropriate. Assess each case individually and refer complicated cases. Refer to SIGN 127 Management of perinatal mood disorders for more information. Initial Review Review every 2-4 until symptom relief, re-assess and record symptoms making use of a validated rating scale like the PHQ9 or HAD score. Titrate drug dose if appropriate. For younger patients on an SSRI, see one week after initiation of therapy to assess for agitation and sideeffects Department of Psychiatry & Prescribing Support Team: March

3 Antidepressant treatment stop or continue? All patients on antidepressants should have their need for antidepressant medication reviewed periodically. Annual reviews of all patients on long term antidepressants should be promoted as best practice in primary and secondary care. Antidepressants reduce the risk of depression recurring by about one half (from an absolute risk of about 40% to 20% in the first year.) Evidence relating to the appropriate duration of treatment is limited. However the guidance below represents an evidence-consistent approach. Antidepressant treatment should be reviewed at 6 months, 12 months and 24 months from recovery. Continued treatment after this time should continue to be reviewed periodically for suitability to stop or continue medication. The decision to stop antidepressant medication is guided by the number of risk factors that may contribute to relapse. These risk factors are: o Current episode was severe, prolonged or treatment-resistant o History of previous episodes (take a careful history) o Continuing residual symptoms o Elderly patients o Ongoing physical health problems and psychosocial difficulties o The consequences are likely to be severe. Prompt, uncomplicate d recovery 1 or more risk factors 2 or more risk factors Stop at 6 months? Stop at 12 months? Stop at 24 (+) months? appropriate: low risk appropriate: low risk appropriate: low risk Advise continue Caution when antidepressant: high stopping: Moderate appropriate: low risk Advise continue antidepressant: high Advise continue antidepressant: high Caution when stopping: Moderate If withdrawal is indicated, reduce dose slowly over 4. Some patients may require, depending on withdrawal effects. Fluoxetine can usually be stopped over a shorter period due to its long half life. (See appendix). This guidance does not apply to people with depression as part of bipolar disorder (manic depression). The dose of antidepressant should be maintained at the level at which acute treatment was effective until a decision is made to stop. Department of Psychiatry & Prescribing Support Team: March

4 Switching Antidepressants 1. Factors to be considered Speed of switch: If possible leave a gap of at least a few between antidepressants. Faster switches may be possible, with specific advice and additional monitoring. Ideally the dose of first drug should be reduced and then stopped. Follow specific advice when swapping to or from an MAOI or Moclobemide. Dose of first drug. Consider the effects of the individual drug (side effects, kinetics, neurotransmitters) Individual susceptibility to (additive) side effects. 2. Potential problems Cholinergic rebound from a drug with cholinergic effects e.g. tricyclics. Symptoms include nausea, vomiting, headache, restlessness. Discontinuation symptoms from first drug which may be interpreted as side effects of second drug e.g. flulike symptoms, insomnia, sensory disturbance, hyper-arousal. Interactions, which may be pharmacodynamic (serotonin syndrome, hypotension, drowsiness) or pharmacokinetic (e.g. elevation of plasma levels of tricyclic antidepressants by some SSRIs). Serotonin syndrome can occur when two drugs both have effects on 5-HT. Symptoms include sweating, diarrhoea, myoclonus, restlessness, shivering, hyper-reflexia, tremor, confusion, convulsions and death. 3. Switching where clinical efficacy is similar: Escitalopram to Citalopram on the grounds of cost effectiveness (if due to QTc prolongation switch to another SSRI, not Citalopram), NB 10mg Escitalopram = 20mg Citalopram Venlafaxine MR to standard release: Standard release should be used first line in all new patients Fluoxetine 60mg: should be prescribed as 3 x 20mg capsules If on.. Cost Switch to Cost Saving Saving per annum Escitalopram 10mg Citalopram 20mg Escitalopram 20mg Citalopram 40mg Venlafaxine 75mg MR Venlafaxine 37.5mg twice daily Venlafaxine 150mg MR Venlafaxine 75mg twice daily Fluoxetine 60mg capsules Fluoxetine 3 x 20mg capsules Antidepressant Cost per Day Cost per Year Tranylcypromine 20mg , Isocarboxazid 20mg Agomelatine 25mg Duloxetine 60mg Venlafaxine (Modified Release) 225mg Phenelzine 60mg Reboxetine 8mg Moclobemide 300mg Lofepramine 140mg Escitalopram 10mg Trazodone 300mg Imipramine 150mg Clomipramine 150mg Venlafaxine (Standard Release) 225mg Sertraline 50mg Amitriptyline 150mg Dosulepin 150mg Paroxetine 20mg Citalopram 20mg Mirtazapine 30mg Fluoxetine 20mg Costs: Drug Tariff and MIMS (Apr 2012) Department of Psychiatry & Prescribing Support Team: March

5 A Guide to Switching Antidepressants Switching Guide adapted by: Wendy Ackroyd with permission from Bazire S. Psychotropic Drug Directory 2012 Lloyd-Reinhold Communications. Updated April 2012 To From MAOIs TCAs* Citalopram / Escitalopram Fluoxetine Sertraline Paroxetine MAOIs TCAs* 7 NSPR CI QTc Great care Great care NSPR NSPR Variable SSP NSPR NSPR Citalopram / 7 CI QTc SSP SSP SSP 7 CI QTc SSP NSPR NSPR Escitalopram Fluoxetine 5 Great SSP SSP SSP 5 SSP NSPR NSPR care for 28 Sertraline 7 Great SSP SSP SSP 4-13 SSP NSPR NSPR Paroxetine 14 Great SSP SSP SSP 5 SSP NSPR NSPR Trazodone 7 OP NSPR SSP NSPR NSPR Moclobemide NSPR OP NSPR 2 WEEKS NSPR NSPR NSPR NSPR SSP NSPR NSPR Venlafaxine 7 NSPR CI QTc NSPR SSP NSPR NSPR Duloxetine 5 SSP SSP SSP SSP SSP SSP SSP SSP NSPR NSPR Mirtazapine 7 NSPR NSPR NSPR NSPR NSPR NSPR NSPR NSPR NSPR NSPR Reboxetine 7 NSPR NSPR NSPR NSPR NSPR NSPR NSPR NSPR NSPR NSPR JUST STOPPING Reduce to 20mg then stop or Refer to current summary of product characteristics (data sheet) for further information and advice. Key 2/52 = two week drug-free gap necessary How to use this table NSPR = No specific problems reported; careful cross-taper 1. Locate first drug in left hand column. SSP = Serotonin syndrome possible with serotonergic drugs. Specific care needed 2. Look across to second drug, to change to. OP = Occasional problems 3. Seek further information if advised. = Cholinergic rebound, interaction or serotonin syndrome possible CI - QTc = contraindicated due to potential QTc prolongation Prescribing Support Team: Dec Trazodone Moclobemide * Refer to SPC for special precautions for clomipramine. Avoid co-administration with SSRIs or Venlafaxine. Venlafaxine or Duloxetine or Mirtazapine Appendix Reboxetine

Volume 4; Number 5 May 2010

Volume 4; Number 5 May 2010 CLINICAL GUIDELINES FOR ANTIDEPRESSANT USE IN PRIMARY AND SECONDARY CARE Lincolnshire Partnership Foundation Trust in conjunction with Lincolnshire PACEF have recently updated