Appendix 4B - Guidance for the use of Pharmacological Agents for the Treatment of Depression in Adults (18 years and over)
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1 Appendix 4B - Guidance for the use of Pharmacological Agents for the Treatment of Depression in Adults (18 years and over) Introduction / Background Treatment comes after diagnosis Diagnosis is based on the history and examination of mental state and may take more than one consultation In typical depressive episodes, the individual usually suffers from low mood, loss of interest and enjoyment, and reduced energy. Other common symptoms include: Disturbed sleep Diminished appetite Reduced concentration and attention Reduced self-esteem and self-confidence Ideas of guilt and unworthiness (even in mild depression) Bleak and pessimistic views of the future Thoughts of suicide or self-harm with suicidal intent The symptoms will have persisted for a minimum of two weeks. The severity of the disorder is determined both by the number and severity of symptoms, as well as the degree of functional impairment Differential diagnosis Consider the following: Normal low mood / sadness Anaemia Check FBC Adjustment disorder Thyroid disease (particularly hypothyroidism) Check TFTs Recent bereavement Anxiety disorder Alcohol or substance misuse Dementia Post viral syndrome Drug side effects Parkinson s disease Bipolar depression etc. Eating disorders Psychotic symptoms Classification of depression Classify into mild, moderate or severe depression. Suggested rating scales include Patient Health Questionnaire 9 (PHQ-9), Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory-II (BDI-II)
2 Assessment of suicide risk Patients considered to be at risk of suicide or under 30 years old should be seen after one week and frequently until risk is considered no longer relevant. All other patients should be seen within 2-4 weeks. Some example questions include: Have you ever felt that life was not worth living? Do you ever wish you could go to sleep and not wake up? Is death something you have thought about recently? All patients should be considered for drug and alcohol misuse. Mild depression Watchful waiting initially for two weeks, then if appropriate consider self-help, cognitive behavioural therapy(cbt), where it is available locally, [6-8 sessions], Interpersonal therapy (IPT), exercise, time structuring and sleep and anxiety management If past history of moderate to severe depression or if persistent or recurrent symptoms despite the above recommendations, consider pharmacological intervention and treat as moderate depression. Consider referral to NHS 24 telephone based guided self help service NHS Living Life. Tel: , available Mon-Fri 1pm to 9pm, calls are free and confidential Moderate/severe depression If patient has previous history of successful treatment, initiate previous therapy if appropriate. antidepressants that the person has previously failed to respond to or could not tolerate Trial of a formulary Selective Serotonin Reuptake inhibitor (SSRI) over at least 6 weeks, with or without psychotherapies listed under mild depression If little or no effect after 2-4 weeks, check compliance, consider increase in dose if partial response bearing in mind most SSRIs are effective at standard dose If no response at 6 weeks confirm diagnosis, then switch to either a different SSRI, or another class of antidepressant, with an awareness of the cautions, contraindications and possible toxicity in overdose If two antidepressants from different classes are ineffective at therapeutic dose for a minimum of six weeks each, then refer for further psychiatric assessment. Severe depression with high suicide risk or psychotic phenomena Refer for further psychiatric assessment Duration of treatment First episode - continue treatment for at least six months (12 months in elderly) after resolution of depression Chronic / recurrent / treatment resistant should be treated for at least two years (lifelong for some). Referral for further psychiatric assessment may be necessary. General guidance on pharmacological treatment All patients must receive information on: Side effects, Time to onset of action, Duration of treatment, Discontinuation / withdrawal effects and importance of follow up / review appointments Consider adding a benzodiazepine for maximum of 1-2 weeks if anxiety increases on SSRIs
3 Choice of antidepressant in patients with specific risk factors or needs Underlying Cardiovascular disease Ischaemic heart disease Arrhythmias Heart block Postural hypotension Tachycardia Recent myocardial infarction (MI) In general most manufacturers advise caution in cardiac disease. Refer to individual SPC for details. SSRIs. Preferred formulary choices are fluoxetine and sertraline. Fluoxetine Sertraline Particularly in elderly patients: Tricyclics Venlafaxine (contraindicated in uncontrolled hypertension and high risk of ventricular arrhythmias) Citalopram - due to the risk of dosedependent QT prolongation, citalopram should not be used in doses above 40mg daily in adults and not above 20mg daily in the elderly (>65 years) or in patients with reduced hepatic function. Contra-indicated in patients with a known QT prolongation or congenital long QT syndrome and in patients who are taking other medicines known to prolong QT interval. Suicide risk or risk of accidental overdose Limiting quantities of medication available e.g. weekly / fortnightly dispensing maybe appropriate Risk of seizures Sertraline* *Manufacturers advise careful monitoring and avoid in unstable epilepsy Tricyclics Venlafaxine Availability of carer / relative support to supervise administration may influence prescribing of the above Fluoxetine
4 Area Drug and Therapeutics Committee Choice of antidepressant in patients with specific risk factors or needs Pregnancy Balance between clinical need and risk in first trimester if possible For information on choice of a suitable antidepressant agent in pregnancy refer to the National Teratology Information Service Also refer to SIGN Guideline 127 Management of Perinatal Mood Disorders, March Discontinuation symptoms may possibly occur in the neonate Breastfeeding Antidepressant choice is made on an individual basis SIGN specifically recommends avoiding fluoxetine and lithium Balance between clinical need and risk If an antidepressant used during pregnancy is to be continued whilst breastfeeding then up to date information regarding the drug safety should be obtained For further information contact specialist Medicines Information Centre drugs in breast milk. Trent Medicines Information Centre. Tel: Also refer to SIGN Guideline 127 Management of Perinatal Mood Disorders, March At risk of Anticholinergic side effects e.g. Constipation Cognitive side effects Dry mouth Exacerbation of glaucoma Urinary retention The elderly are more susceptible to such side effects. For antidepressants less likely to cause anticholinergic side effects: SSRI (Formulary options). Venlafaxine Sedation Sexual dysfunction Particularly in elderly patients: Tricyclics For patients requiring sedation Without cardiac history, risk/history of With cardiac history, risk of suicide or seizures or risk of suicide anticholinergic side effects Tricyclics All drugs acting on the central nervous system can impair alertness, concentration and driving performance, particularly at initiation and on dose alteration. Advise that driving must cease if adversely affected. For patients experiencing sexual adverse effects of antidepressant SSRIs
5 Key features of Fife Formulary antidepressants Drug Class Useful features Potential problems and side effects Selective serotonin reuptake inhibitors (SSRIs) Fluoxetine Sertraline Less sedating and less likely to be fatal if taken in overdose Starting dose is normally therapeutic dose May worsen anxiety / insomnia in short term Gastrointestinal (GI) side effects, headache Discontinuation phenomena (less likely with fluoxetine). SSRIs may increase the risk of serious GI bleeding. This risk should be considered when selecting an antidepressant for the elderly, particularly those over 80 years or for patients with a history of GI bleeding or taking aspirin or NSAIDs. Tricyclics (TCAs) Clomipramine Imipramine (S) Noradrenergic and specific serotonergic antidepressant (NASSA) Serotonin and Noradrenaline reuptake inhibitors (SNRIs) Venlafaxine Sedation can be useful for patients with agitation and sleep problems Clomipramine is useful for patients with obsessional or phobic features Sexual dysfunction is less common Less likely to be fatal if taken in overdose Sedating (more so at lower doses) thus useful for patients with sleep problems Useful for patients with depression accompanied with anxiety Toxic in overdose Cardiovascular side effects arrhythmias, postural hypotension, tachycardia contraindicated in recent myocardial infarction, arrhythmias (particularly heart block) Anticholinergic side effects blurred vision, dry mouth, constipation urinary obstruction Dose requires to be gradually titrated Increased appetite and weight gain can be troublesome May rarely cause blood dyscrasias Contraindicated in patients with uncontrolled hypertension and in patients with high risk of serious cardiac ventricular arrhythmias Requirement for ongoing monitoring of blood pressure (at least six monthly) Switching and stopping antidepressants When switching from one antidepressant to another, be aware of: The need for gradual and modest incremental increases in dose Interactions between antidepressants The risk of serotonin syndrome if there are combinations of serotonergic antidepressants prescribed For further guidance refer to Appendix 4E Antidepressants Swapping and Stopping Serotonin syndrome symptoms Restlessness Excessive sweating Tremor Shivering increasing severity Myoclonus Confusion Convulsions Death Stopping or reducing antidepressants When stopping or reducing antidepressants:
6 Inform patients about the possibility of discontinuation / withdrawal symptoms on missing doses of drugs with short half-life, or when reducing or stopping medication. They are usually mild and self-limiting but occasionally can be severe if the drug is stopped abruptly Reduce dose gradually over at least a four week period but some people may require longer periods. Withdrawal symptoms are particularly apparent with Paroxetine or venlafaxine. Fluoxetine which has a long half-life can usually be reduced and stopped over a shorter period For mild discontinuation / withdrawal symptoms reassure the patient and monitor symptoms For severe symptoms consider reintroducing the original antidepressant at the previous dose (or another antidepressant with a longer half life from the same class) and reduce gradually while monitoring symptoms Antidepressant discontinuation symptoms Drugs most commonly associated with discontinuation symptoms TCAs Common Flu-like symptoms (chills, myalgia, excessive sweating, headache, nausea), insomnia, excessive dreaming Occasional Movement disorders, mania, cardiac arrhythmias Amitriptyline Imipramine (S) SSRIs and related Common Flu-like symptoms, electric shock like sensations, dizziness exacerbated by movement, insomnia, excessive (vivid) dreaming, irritability, crying spells Occasional Movement disorders, problems with concentration and memory Venlafaxine Key counselling points for prescribers initiating antidepressants The following common concerns should be discussed with patients prior to initiation of an antidepressant: What is an antidepressant? Delayed effect Duration of treatment Antidepressants are not addictive An antidepressant is a drug which is used to treat depression by altering chemical(s) in the brain It is not a tranquiliser or a sleeping tablet Improvement may be seen within the first week of treatment and will continue to build over 4-6 weeks In first episode it is recommended that treatment should continue for at least six months after remission. Joint decision between patient and prescriber to discontinue treatment. Antidepressants are not associated with tolerance or craving but discontinuation effects may occur Discontinuation effects Discontinuation effects may occur on stopping, missing doses or occasionally on dose reduction.
7 Side effects Akathisia, suicidal ideas, and increased anxiety and agitation Over the counter medicines Alcohol and antidepressants Driving Follow up Area Drug and Therapeutics Committee This is particularly so with paroxetine and venlafaxine Antidepressants are usually reduced over several weeks. Side effects may occur before clinical improvement, some may diminish with time. Advise patients of these symptoms particularly in the early stages of treatment with an SSRI or SNRI. Advise patient to seek help promptly if these are at all distressing Confirm if the patient is taking any over the counter medication (including herbal remedies). Check for possible interaction with antidepressant drugs. St John s Wort interacts with antidepressants Advise caution if drinking alcohol while taking antidepressants. Limit alcohol to small amounts. Never drive if taking antidepressants and alcohol Do not drive if feeling drowsy or sedated by antidepressant medication Agree follow up arrangements with patient Patient information leaflets can be downloaded from NHS Inform:
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