4.3 Antidepressants (ADDs) BNF Section 4.3

Transcription

1 4.3 Antidepressants (ADDs) BNF Section 4.3 The aim of this guidance is to provide prescribing guidance and highlight good practice. It is not intended to be a comprehensive practice treatment guideline. Treatment of Depression (from NICE 2009)!PRESCRIBE GENERICALLY! First line: (For Special Patient groups, including children, see below) A Selective Serotonin Reuptake Inhibitor (SSRI) in generic form citalopram or fluoxetine or sertraline Second line: (If first choice ineffective or poorly tolerated) Third line: If patient also has a chronic physical health problem: A different SSRI from the list above or a better tolerated newer generation antidepressant e.g. mirtazapine. Less well tolerated newer generation antidepressant e.g. venlafaxine Consider the side effect profile of the individual antidepressant; the presence of additional physical health disorders and interaction profile with concomitant prescribed medicines. PRESCRIBING NOTES MONITORING COST of prescribing (1 year) EVIDENCE New Patients: If a new patient presents with apparent depression please consider whether there are any contributory/aggravating causes, e.g.: Psychosocial or physical. Is the patient taking drugs that may cause depression? (Including excessive caffeine intake). Hyperthyroidism, hypothyroidism Check the patient s TFTs (Thyroid Function tests). C&W APC Approved Guideline [CG013] Published: Jun 2012 Review date: Jun 2013

2 PRESCRIBING NOTES: - Dose Choice of antidepressant Contra-indications Limited response to initial treatment Duration of Treatment Switching antidepressants Discontinuation Patient Counselling Antidepressants In Special Patient Groups Existing chronic physical health problems Potential side effects Dose(listed alphabetically) For individual data sheets see electronic Medicines Compendium Antidepressant (click to link to BNF) Class Initial Dose (Adult) see BNF for doses for older adults or children) Adult Maximum Daily Dose NB. Use the lowest effective dose. (See BNF for dosing scheme, and doses for older adults/children). Half-life (hours) Peak plasma concentr ation (hours) Active metabolite? citalopram (citalopram has the lowest propensity for drug interactions) SSRI 20mg once daily 40mg fluoxetine (fluoxetine has the longest half-life and therefore least likely to be associated with withdrawal issues). SSRI 20mg once daily 60mg Yes mirtazapine An NaSSA (noradrenergic and specific serotonergic antidepressant) 15mg daily at bedtime sertraline SSRI 50mg once daily venlafaxine SNRI 37.5mg twice daily 45mg mg Yes 375mg (2-7) Yes In responders improvement occurs in more than 70% of cases within the first 3 weeks of treatment. (For partial response see Limited response to initial treatment). See NICE CG90 Depression for the stepped care approach model: This guidance focuses on the pharmacological management of the treatment of depression. Psychological therapies are the first line option for mild depression. Antidepressants should not be prescribed routinely to treat persistent sub-threshold symptoms or mild depression. However, they should be considered for people with A past history of moderate or severe depression, or Initial presentation of sub threshold depressive symptoms that have been present for a long period (typically at least 2 years), or

3 Sub threshold depressive symptoms or mild depression that persists after other interventions. Choice of Antidepressant: All the main antidepressants appear to have broadly similar efficacy. Antidepressant choice should therefore be based on the following: Features of depression Suicide risk Concomitant therapy Concurrent illness (see below) Side-effect tolerability Time to reach therapeutic dose Cost Effectiveness Special considerations (e.g. driving) Patient preference If prescribing agents other than SSRIs, consider the increased likelihood of the person stopping treatment because of side effects the requirement to increase dose gradually with venlafaxine, duloxetine and the TCAs; the specific cautions, contraindications and monitoring requirements Risk of overdose i.e. tricyclic antidepressants, venlafaxine If the recommendations are unsuitable/ineffective please note the following further treatment choice options (listed alphabetically) (also consider the Preferred Prescribing List) : Duloxetine (an SNRI) - Relative lack of data on side-effects compared to established drugs. Moclobemide (a reversible MAOI) - If switching to this need wash out period in-between. Phenelzine (an MAOI) - Specialist initiation only (see below). Consider for patients who have failed to respond to alternative antidepressants and who are prepared to tolerate the side effects and dietary restrictions. (NB. Consider toxicity risk in overdose). Tricyclic Antidepressants (TCAs) - but not dosulepin (NOT recommended - see below) o Poorer tolerability compared to other equally effectives ADDs. Increased risk of cardiotoxicity (with the exception of lofepramine which has a relative lack of cardiotoxicity). Toxicity in overdose - more dangerous in overdose than the SSRIs. Venlafaxine (an SNRI) Venlafaxine may exacerbate hypertension. Regular blood pressure monitoring required for all patients. It should be used with caution in established cardiac disease; the balance of risks and benefits should be considered before prescribing venlafaxine to patients at high risk of serious cardiac arrhythmia. At doses of 300mg daily and above, venlafaxine should only be initiated by specialist mental health medical practitioners, including General Practitioners with a Special Interest in Mental Health. The preferred formulation is standard release tablets. Please note that the following medications (listed alphabetically) are not generally recommended: Agomelatine (melatonin receptor agonist and selective antagonist action at serotonin receptor). Relatively new on the market. Relative lack of data on side-effects compared to established drugs. Liver

4 monitoring is required on initiation (see monitoring section).reviewed by D&T. Escitalopram Reviewed by D&T. Use deemed unjustifiable at present for the treatment of depression in view of its higher cost with no significant clinical advantage over citalopram. Paroxetine - associated with more discontinuation/withdrawal symptoms. The following medications should not be prescribed: Dosulepin the most cardio-toxic of the TCAs. Marked TOXICITY in OVERDOSE. ( NICE guidance) St Johns Wort not recommended because of uncertainty about appropriate doses, variation in the nature of the preparations and potential serious interactions with other drugs Contra-indications: See BNF links below &/or specific data sheets at electronic Medicines Compendium TCAs: MAOIs SSRIs* Other antidepressants BNF TCA advice BNF MAOI Advice BNF SSRI Advice BNF Advice Other Antidepressants *Following a study revealing a dose dependent increase in QT interval, the MHRA has (December 2011) issued a Drug Safety Advice Report which addresses the revised cautions/contraindications for both citalopram and escitalopram. Both drugs are now contraindicated in patients with congenital long QT syndrome or known pre-existing QT interval prolongation, or in combination with other medicines known to prolong the QT interval. This includes class IA and IIIA antiarrhythmics (e.g. amiodarone, quinidine), antipsychotics, tricyclic antidepressants, some antimicrobial agents, some antihistamines, some antiretrovirals. Some medications (e.g. omeprazole, cimetidine) may increase plasma levels of citalopram/ escitalopram. This may require a dose reduction of citalopram/escitalopram. If citalopram/escitalopram is prescribed with agents listed above, such prescribing would be outwith the product license due to the contraindication. A risk/benefit assessment should be undertaken and documented. There is a checklist available on the CWPT Medicines Management intranet site which may help with this assessment. QT prolongation may also (rarely) occur with other SSRI antidepressants. However, as a class, they are still significantly safer regarding cardiotoxicity than tricyclic antidepressants. If limited response to initial treatment: Check compliance, consider dose increase (if some response at lower dose, and side-effects allow), consider switching antidepressant if there has been no response after a month. If there has been a partial response, a decision to switch can be postponed until 6 weeks. See NICE for more in-depth information. In older adults the dose should be given for a minimum of 6 weeks before the antidepressant is considered ineffective. If there is partial response within this period, treatment should be continued for a further 6 weeks. Augmentation strategies may be useful in patients who have failed to respond to the third line suggestions above. If so, prescribers should be aware of the likely increased side-effects; should discuss the rationale with the patient; monitor carefully for adverse effects; follow the Trust procedure for unlicensed prescribing if appropriate; consider the evidence base and monitor for efficacy; should document all relevant information clearly in the medical notes. NICE suggests augmentation with lithium, an antipsychotic (e.g. aripiprazole, olanzapine, quetiapine or risperidone) or another antidepressant (e.g. mirtazapine or mianserin). NICE does not recommend augmenting with A benzodiazepine for more than 2 weeks (risk of dependence) Buspirone, carbamazepine, lamotrigine or valproate (insufficient evidence for their use) Pindolol or thyroid hormones (inconsistent evidence of effectiveness)

5 Duration of Treatment: For patients with moderate or severe depressive episode antidepressants should be continued for at least 6 months after remission. (Patients who have had two or more depressive episodes in the recent past, and who have experienced significant functional impairment during the episodes, should be advised to continue antidepressants for 2 years. To prevent relapse dose should be maintained at the level at which acute treatment was effective). When deciding whether to continue maintenance treatment beyond 2 years, re-evaluate with the patient, taking into account age, comorbid conditions and other risk factors. Potential side effects: See BNF links below and/or specific data sheets at TCAs are noted for their association with antimuscarinic side-effects, such as dry mouth and constipation. They may also be associated with a risk of cardiotoxicity in overdosage. The SSRIs have fewer antimuscarinic side-effects than the older tricyclics and they are also less cardiotoxic in overdosage. They do, however, have characteristic side-effects of their own; gastrointestinal side-effects such as nausea and vomiting are common and bleeding disorders have been reported (higher risk when combined with non-steroidal anti-inflammatory drugs). They have also been reported to be associated with an increased risk of suicide during the first month of treatment compared to other antidepressants. All prescribers should have an awareness of serotonin syndrome. Features of serotonin syndrome include confusion, delirium, shivering, sweating, changes in blood pressure and myoclonus. This is due to a serotonergic surge, which is caused by one or more agents which increase serotonin levels. Drugs associated with serotonin syndrome include: Monoaminoxidase inhibitors (MAOIs) Tricyclic antidepressants SSRIs (Selective Serotonin Reuptake Inhibitors) SNRIs (Serotonin and noradrenaline reuptake inhibitors) Trazodone Lithium St John s Wort Tryptophan Buspirone Carbamazepine Sumatriptan Tramadol Pethidine (and other opioids) Dextromethorphan (found in some cough mixtures) All patients (and carers) should be alerted to monitor for the emergence of suicidal ideation/behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present. TCAs (and related): MAOIs SSRIs Other antidepressants BNF TCA advice BNF MAOI Advice BNF SSRI Advice BNF Advice Other Antidepressants CSM Advice - Hyponatraemia and antidepressant therapy. Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants; however, it has been reported more frequently with SSRIs than with other antidepressants. The CSM has advised that hyponatraemia should be considered in all patients who develop drowsiness, confusion, or convulsions while taking an antidepressant.

6 o In the event of hyponatraemia the antidepressant should be withdrawn immediately (note risk of discontinuation effects). o If serum sodium >125mmol/l monitor sodium daily until normal o If serum sodium <125mmol/l refer to specialist medical care. (Contact the Medicines Management Team for further info.) Switching antidepressants. When switching from one antidepressant to another, prescribers should be aware of the need for gradual and modest incremental increases of dose, of interactions between antidepressants and the risk of serotonin syndrome when combinations of serotonergic antidepressants are prescribed. Other problematic problems on switching may also include cholinergic rebound and antidepressant withdrawal symptoms. For up to date advice on specific switches, contact the Medicines Management Team. Discontinuation: To reduce the possibility of discontinuation/withdrawal symptoms reduce doses gradually over a 4-week period; (some people may require longer periods. Fluoxetine can usually be stopped over a shorter period; drugs with a shorter half life, e.g. paroxetine, venlafaxine are more likely to cause discontinuation symptoms). Switching to a liquid formulation can enable dose reductions to be made in smaller steps In the event of mild discontinuation/withdrawal symptoms, reassure the patient & monitor symptoms. Severe symptoms: consider reintroducing the original ADD at the effective dose (or another ADD from the same class with a longer half-life-but be aware of risk of precipitating serotonin syndrome if this option is chosen). Reduce gradually while monitoring symptoms. Patient Counselling: Discuss with patients/carers information about: nature, course and treatment of depression, including the use and likely side-effects of medication and when to report back; any concerns/perceptions they have about the proposed treatment. Discuss any response/compliance to antidepressants in the past. Also discuss issues about the delay in onset of effect, the time course of treatment and the need to take medication as prescribed. Also discuss that, although the drugs are not associated with tolerance and craving, discontinuation/withdrawal symptoms may occur on stopping, missing doses or, occasionally, on reducing the dose of the drug. These symptoms are usually mild and self-limiting but can occasionally be severe, particularly if the drug is stopped abruptly. Information to patients to help support advice given is available on the Choice and Medication Website (can be accessed via Trust intranet/internet home pages). Easy read leaflets are also available, which may help support people with learning disabilities. Antidepressants In Special Patient Groups Evidence based data is limited. The information below is given as suggested guidance. However, the choice of antidepressant depends on an assessment of the individual patient. Please contact a member of the Medicines Management team for more in-depth information/alternative options or for other disease states. NB: SSRIs increase the risk of gastro intestinal (GI) bleeding; therefore patient should be assessed for risk factors (e.g. older adult, concurrent medication (see chronic physical health problems), history of GI bleeds) Breast-Feeding: contact Medicines Management for patient specific information.

7 Also see BNF. Cardiovascular disease: sertraline (Recent myocardial infarction or unstable angina) Children and Adolescents NICE has made recommendations for the identification and treatment of depression in children (5 11 years) and young people (from the age of 12 up to their 18th birthday) in primary, community and secondary care. The guidelines recommends that: Antidepressant medication should not be used for the initial treatment of children and young people with mild depression Children and young people with moderate to severe depression should be offered psychological therapy as a firstline treatment Antidepressant medication should only be offered to children or young people with moderate to severe depression in combination with a concurrent psychological therapy. Fluoxetine is the only antidepressant for which trials show that the benefits of treatment outweigh the risks. Diabetes: sertraline Epilepsy: citalopram or sertraline The patient s anticonvulsant regimen should be checked for potential drug-induced depression (consider changing anticonvulsant). If an antidepressant is prescribed it should be introduced gradually, starting with a low dose, and not exceeding the maximum. Hepatic Impairment Contact Medicines Management for patient specific information. Reference sources cite different preferred agents, dependent on degree of impairment. Many ADDs are metabolised by the liver. Start on lower doses, and increase more gradually than normal (risk of accumulation and therefore toxicity is greater as the degree of impairment increase). Learning Disabilities Existing evidence suggests that the efficacy and effectiveness of treatment of depression of people with LD is very similar to the treatment of depression in the general population; however, consider co-existing conditions e.g. epilepsy. The presentation of depression may be different. Old Age: citalopram or sertraline Depression in dementia patients should be treated in the same way as depression in other older adults. SSRI use is associated with an increased risk of bleeding (see chronic physical health) - physicians therefore need to assess the risk vs. benefit balance for each individual patient. There is an increased risk of hyponatraemia in older adults. Should avoid agents with sedative properties that may increase the risk of falls. Also consider the risk of GI bleeds with SSRIs; risk of QTc prolongation with citalopram/escitalopram. Consider lower starting doses. Pregnancy: contact Medicines Management for patient specific information. Also see BNF. Renal Impairment: citalopram or sertraline Start with a low dose, titrate slowly and monitor patients closely. Side effects may be enhanced. Extra caution may be needed when switching between antidepressants as half lives may be extended.

8 Medication for people with a chronic physical health problem Non steroidal antiinflammatory drugs (NSAIDs) NICE (CG 91) Recommended choice of antidepressant Do not normally offer SSRIs; if no suitable alternative, offer gastroprotective medicine (e.g. proton pump inhibitor such as lansoprazole, omeprazole) with the SSRI (risk of gastrointestinal bleeding is increased six times with concomitant use) Consider mianserin, mirtazapine, moclobemide or trazodone Warfarin and heparin Aspirin Do not normally offer SSRIs Consider mirtazapine (NB with warfarin, INR may increase slightly) Use SSRI with caution, together with a gastroprotective medicine if no suitable alternatives can be identified Consider trazodone, mianserin, mirtazapine Triptan drugs for migraine Theophylline, clozapine, methadone or tizanidine Flecainide or propafenone Atomoxetine Do not offer SSRIs Offer mirtazapine, mianserin Do not normally offer fluvoxamine Offer sertraline Offer sertraline as the preferred antidepressant Mirtazapine and moclobemide may also be used Do not offer fluoxetine or paroxetine Offer a different SSRI Co-existing Chronic Physical Health Problems

9 MONITORING: -

10 Baseline/Early Monitoring NICE (2009) Recommended Patient Review Intervals: Patients considered to be at increased risk of suicide or who are younger than 30 years old: See one week after starting treatment (Any non-attendance should be followed up). Monitor frequently until the risk is no longer significant. (If there is a high risk of suicide, prescribe a limited quantity of antidepressants, consider choice of antidepressant, and consider additional support). Patients not considered to be at increased risk of suicide: See 2 weeks after starting treatment and regularly thereafter for example, every 2 4 weeks in the first 3 months reducing the frequency if response is good. Recommended monitoring: Side-effects especially akathisia, suicidal ideas, and increased anxiety and agitation, particularly in the early stages of treatment with an SSRI. (Patients at risk of these symptoms should seek help promptly if these are at all distressing). If increased agitation develops early in treatment with an SSRI, provide appropriate information and, if the patient prefers, either change to a different antidepressant or consider a brief period of concomitant treatment with a benzodiazepine followed by a clinical review within 2 weeks. Compliance Improvement in Clinical Signs and Symptoms - Continued monitoring is important if a patient experiences worsening of symptoms or new symptoms after starting treatment. Patients should also be monitored around the time of dose changes for any new symptoms or worsening of disease. U&Es LFTs BP and Pulse Specific Advice: SSRIs The Medicines and Healthcare products Regulatory Agency (MHRA) published guidance on use of SSRIs and related drugs in December The guidance concluded that SSRIs continue to have a positive balance of benefits to harms in their licensed indications. It gave updated general advice on prescribing, and in three specific areas - withdrawal reactions, dose changes, and suicidal behaviour. The group also made recommendations on the prescribing of venlafaxine, because of its potential for cardiotoxicity and greater toxicity in overdose (see below). Citalopram/Escitalopram: Patients with cardiac disease - Consider an ECG before treatment. An ECG should also be undertaken (in any patient) if cardiovascular symptoms (e.g. palpitations, vertigo, syncope or seizures) develop during treatment. Patients should be advised to contact a healthcare professional immediately if they experience an abnormal heart rate or rhythm while taking citalopram or escitalopram. U&Es: check and correct any electrolyte disturbances, (including hypokalaemia and hypomagnesaemia) - prior to treatment, and during treatment for elderly patients prescribed diuretics or proton pump inhibitors. Venlafaxine: Undertake regular monitoring of blood pressure. For patients experiencing sustained increase in blood pressure either dose reduction or discontinuation should be considered. Pre-existing hypertension should be controlled before treatment with venlafaxine. Measurement of serum cholesterol levels should be considered during long-term treatment. Mirtazapine - Full Blood Count: Bone marrow depression, which is usually manifested by granulocytopenia or agranulocytosis, has been reported in the users of mirtazapine. This effect is usually seen after 4-6 weeks of treatment, but it usually disappears after discontinuation of treatment. Reversible agranulocytosis has also been reported in rare cases in clinical trials on mirtazapine. The patient should be advised to contact a doctor if there is emergence of fever, throat pain, stomatitis and other signs and symptoms suggestive of infection. If these manifestations occur, the treatment must be discontinued and a complete blood count should be taken. Agomelatine - LFTs at baseline, 6, 12 and 24 weeks, and as clinically indicated thereafter. Lithium (as augmentation) see separate lithium prescribing guidance and shared care agreement Annual Improvement in Clinical signs and symptoms, Side-effects, Compliance, U&Es, Thyroid function and LFTs.

11 COST: 1 year Notes Soluble tablets and liquids should only be prescribed where tablets are not suitable as these formulations are usually significantly more expensive. Medicines Management Escitalopram oral drops 20mg/ml 20mg OD Fluoxetine caps 60mg OD (1 by 60mg) Escitalopram tabs 20mg OD Paroxetine liquid 10mg/5ml 20mg OD Escitalopram tabs 10mg OD Citalopram oral drops 40mg/ml 40mg OD Fluvoxamine tabs 100mg OD Fluoxetine liquid 20mg/5ml 20mg OD Citalopram oral drops 40mg/ml 20mg OD Fluvoxamine tabs 50mg OD Sertraline tabs 100mg OD Sertraline tabs 50mg OD Fluoxetine caps 60mg OD (3 by 20mg) Citalopram tabs 20mg OD Citalopram tabs 40mg OD Paroxetine tabs 30mg OD Paroxetine tabs 20mg OD Citalopram tabs 10mg OD Fluoxetine caps 20mg OD Selective serotonin re-uptake inhibitors BNF 4.3.3: Cost for 1 year Drug Tariff Dec 2011 / BNF Sept 2011 Doses given for costing purposes only & do not imply therapeutic equivalence Note cost differential between citalopram and escitalopram Costs for 1 year Sertraline: The price of sertraline has returned to near normal levels (after a temporary shortage) - as per Jan 12 Drug Tariff 637 Note cost differential between 3 by 20mg fluoxetine and 1 by 60mg

12 Medicines Management Venlafaxine XL caps (Efexor) 300mg OD (2 by 150mg) Agomelatine tabs 50mg OD Tryptophan tabs 1g TDS (6 by 0.5g) Venlafaxine XL caps (Efexor) 75mg OD Mirtazapine oral soln 15mg/ml 30mg OD Venlafaxine XL caps (Efexor) 150mg OD Venlafaxine MR tabs (Venlalic) 300mg OD (2 by 150mg) Venlafaxine MR tabs (Venlalic) 225mg OD Agomelatine tabs 25mg OD Duloxetine caps 60mg OD Duloxetine caps 30mg OD Reboxetine tabs 4mg BD Venlafaxine MR tabs (Venlalic) 150mg OD Venlafaxine MR tabs (Venlalic) 75mg OD Venlafaxine standard tabs 150mg BD (2 by 75mg) Venlafaxine standard tabs 75mg BD Mirtazapine tabs 45mg OD Mirtazapine tabs 15mg OD Flupentixol tabs 2mg OD (2 by 1mg) Venlafaxine standard tabs 37.5mg BD Mirtazapine oro disp tabs 45mg OD Mirtazapine oro disp tabs 15mg OD Mirtazapine tabs 30mg OD Mirtazapine oro disp tabs 30mg OD Flupentixol tabs 1mg OD Other antidepressants BNF 4.3.4: Cost for 1 year Drug Tariff Dec 2011 / BNF Sept 2011 Doses given for costing purposes only & do not imply therapeutic equivalence reboxetine not recommended Costs for 1 year Standard twice daily venlafaxine substantially cheaper than modified release. Consider whether modified relaease (once or twice daily) warrants additional costs. If using once daily modified release, prescribe as Venlalic MR tablets, as most cost effective ,000 1,200 Medicines Management Imipramine oral solution 25mg/5ml 150mg OD Amitryptyline oral solution 50mg/5ml 150mg OD Trazodone liquid 50mg/5ml 150mg OD Imipramine oral solution 25mg/5ml 75mg OD Mianserin tabs 90mg OD (3 by 30mg) Amitryptyline oral solution 25mg/5ml 75mg OD Lofepramine oral solution 70mg/5ml 70mg BD Nortriptyline tabs 75mg OD (3 by 25mg) Doxepin caps 150mg OD (3 by 50mg) Mianserin tabs 30mg OD Trimipramine tablets 75mg OD (3 by 25mg) Lofepramine tabs 70mg BD Doxepin caps 75mg OD (3 by 25mg) Clomipramine SR tabs 75mg OD Imipramine tabs 150mg OD (6 by 25mg) Clomipramine caps 75mg OD (3 by 25mg) Trazodone tabs150mg OD Imipramine tabs 75mg OD (3 by 25mg) Amitriptyline tabs 150mg OD Amitriptyline tabs 75mg OD (3 by 25mg) Dosulepin tabs 150mg OD (2 by 75mg) Dosulepin tabs 75mg OD Tricyclic and related antidepressants BNF 4.3.1: Cost for 1 year Drug Tariff Dec 2011 / BNF Sept 2011 Doses given for costing purposes only & do not imply therapeutic equivalence ,000 1,200 1,400 1,600 1,800 1,054 1,323 Limit liquid use 1,533 Costs for 1 year Avoid dosulepin (dothiepin) - danger in overdose and BNF recommends issuing as max of 14 day supply

13 Evidence/ References: - NICE Clinical Guidance 90 (2009) NICE Clinical Guidance 91 (2009) NICE Clinical Guidance 28 (2005) BNF 61 March 2011 Depression Depression with a chronic physical health problem Depression in children and young people Electronic Medicines Compendium at Eyding D, et al. Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials. BMJ 2010;341:c Reboxetine a striking example of publication bias The Frith Prescribing guidelines for adults with intellectual disability.2008 S Bhaumik, D Brandford. 2 nd Edition. Healthcomm Psychotropic Drug Directory 2010, S.Bazire. Lundbeck The Maudsley Prescribing Guidelines 10 th Edition. Informa Healthcare. UKMI Q&A If antidepressant-induced hyponatraemia has been diagnosed, how should the depression be treated? UKMI Q&A 24.4 What is the most appropriate antidepressant to use in epileptics? Sept 2010 UKMI Q&A What is the first choice antidepressant for patients with renal impairment? Feb 2011 Committee on Safety of Medicines Review (CSM), December Updated prescribing advice for venlafaxine (Efexor/Efexor XL): Information for healthcare professionals 31 May Drug Safety Update Volume 5, Issue 5, December 2011 Other Useful Contacts: Medicines Management Team, based at Wayside House, Coventry