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Home , Citalopram, Sertraline

Guidance for the treatment of depression in adults

MILD DEPRESSION - Medication is not first-line treatment or only treatment for depression  Actively monitor symptoms, give life style advice, guided self- help or exercise MODERATE DEPRESSION

 Consider psychological intervention. This is accessed by referral or self-referral to Mid Essex IAPT (Improving Access to Psychological Therapies) and include Cognitive Behavioural Therapy (CBT) or Interpersonal Therapy (IPT)

Ask about OTC/Herbal/St John’s Wort use – NO SSRI to be prescribed if already on St John’s Wort or stop St John’s Wort Consider referral to specialist care early if the patient has significant , severe depression, depression in .

MODERATE to SEVERE DEPRESSION Discuss medication and treatment options with patient before prescribing, include and risk of suicidal thoughts during onset of treatment. Consider patients co-morbidities when selecting and ask about OTC/Herbal/St John’s Wort as described above. Refer to IAPT - Psychological therapies should be continued alongside medication. Ensure adequate duration of treatment has been tried before switching medication or increasing dose.

CITALOPRAM 20mg daily or 50mg daily – consider Dose 10mg for 10days then Assess efficacy over 6-8 weeks. If effective see box 1 titration 20mg for 6-8 weeks

Ineffective Sertraline – consider Poorly 25mg for 10days then tolerated 50mg for 6-8 weeks Increase to:

Citalopram 30mg OD, Switch to or increase to 40mg after 6 line another SSRI or .

st weeks if required (MAX dose 1 Cross-taper when switching. Box 1. in elderly = 20mg) Increase to therapeutic dose. Sertraline 100mg OD, WHERE increase to 150mg after 6 Assess over 4-6 weeks TREATMENT weeks if required If effective see box 1 IS EFFECTIVE Assess over 4-6 weeks If effective see box 1 Continue for 4-6 Ineffective or Poorly months at same Ineffective tolerated dose. or Poorly tolerated  Elderly 1 year.  In recurrent  tablets 37.5mg – 225mg: depression 2 Switch to fluoxetine Check cardiac status and BP at initiation. years. or another SSRI or Check BP 1 week after a dose change Mirtazapine. Cross- Poorly

tolerated If once daily modified release is required prescribe Vensir XL taper when Then slowly taper (prolonged release) when possible. dose down and line

switching.

d  antidepressant – 70mg-210mg n Increase to stop. 2 (least cardiotoxic TCA) therapeutic dose. If effective see box 1 (see Appendix 1) Assess over 4-6 weeks If effective see box 1 Ineffective or Poorly tolerated Refer to specialist if not already referred

Any 2nd line agent not already tried OR refer for one of the following Specialist initiation only treatments: ECT  Venlafaxine above 300mg – ECG and BP monitoring  For very Combination of SSRI and mirtazapine  severe and

 Augmentation with or Sertraline line

treatment

resistant 3rd  – need full counselling on MAOI interactions. Second line option in atypical depression depression  - in refractory/severe depression or psychotic depression (INPATIENT)Page 1 of 6 DepressionGUI201611V2 0FINAL If effective see box 1

Restricted Anti-depressants that do not appear in the flow chart are non-formulary if you are asked to prescribe refer back to the Medicines Optimisation/Management Team.

General principles in treatment of depression

Evidence shows that patients who are diagnosed with depression face a significant risk that their depression will recur over time and those repeated episodes become more difficult to treat. This highlights the importance of treating the initial episode adequately in conjunction with psychological therapy and reviewing the patient in order to reduce the risk of subsequent depressive episodes.

Mild depression — Antidepressants should not be prescribed for mild depression due to the poor risk-benefit ratio and evidence that for many people with mild depression, there is little clinically-relevant difference between treatment with an antidepressant and . Antidepressants may be considered for people with mild depression with persistent symptoms despite following other interventions.

Moderate-to-severe depression — antidepressants are effective for treating people with moderate or severe depression.

Prescribing antidepressants is only one aspect in the recovery process in the treatment of depression.

When starting an antidepressant:

Consider risk and toxicity in overdose. Patients, (especially those aged 30 years and under), should be asked directly about suicidal ideation and intent to harm, particularly during high-risk periods such as during initiation of, and changes to, medication. A maximum of one week’s medication should be considered for those assessed at risk. Caregivers should be aware of the need to monitor for the emergence of suicidal thoughts and behaviour and seek medical advice immediately, especially at the start of treatment, during dose changes and when antidepressant treatment is being changed.

Explain that symptoms of may initially worsen. Explain that antidepressants take time to work. Explain that antidepressants should be continued for at least 6 months following remission of symptoms, as this greatly reduces the risk of relapse.

Follow up: The review period should be determined by the risk of suicide and the need to assess the tolerability and effectiveness of any treatments started or changed. In general, for people not considered to be at an increased risk of suicide:  Arrange an initial review: o Within 1 week for people less than 30 years of age who have been started on an antidepressant. o Within 2 weeks for other people.  Arrange subsequent reviews every 2–4 weeks for the first 3 months and if the response to treatment is good, longer review intervals can be considered.

Treatment Duration Patients with a single episode should be treated for at least 6 months (as an absolute minimum) after resolution of symptoms. Those who have experienced multiple episodes in the recent past should be advised to continue antidepressants for at least two years after remission.

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Other physical co-morbidities If the person has a chronic physical health problem: Sertraline may be preferred, because it has a lower risk of drug interactions. If an SSRI is prescribed, consider gastro-protection in older people who are taking non-steroidal anti-inflammatory drugs (NSAIDs) or .

Coronary Heart SSRIs are the agents of choice in CHD. They are generally well tolerated, effective and safe to use in patients with CHD when appropriate precautions are taken. Sertraline is safe post MI and considered the drug of choice in these patients.

Cardiac rhythm disorders—QT interval prolongation Some SSRIs are associated with prolongation of the QT interval on the ECG trace. Citalopram prolongs the QT interval in a dose-dependent fashion. To a lesser extent, the concern has also been raised for fluoxetine. Sertraline is associated with QT interval prolongation but the evidence is less well established. There is little compelling evidence that recommended doses of other SSRIs prolong the QT interval.

Prolongation of QT interval can, in rare cases, result in ventricular tachyarrhythmias such as potentially life- threatening torsades de pointes and in sudden death or Sudden and transient loss of consciousness (syncope).

Citalopram should not be used with other drugs that prolong the QT interval. In patients at particular risk of QT-interval prolongation citalopram or fluoxetine should either be avoided or used with caution and after assessing the ECG and measuring plasma electrolytes. These patients should continue to be watched for signs and symptoms of during treatment. ECG assessment should be considered when increasing the dose of the antidepressant.

Side effects

Many side effects can occur, the common ones being , anxiety and sleep disturbance. Side effects usual last no more than 14 days – patients should be reassured of this and explained. If necessary reduce the dose and re- titrate up again gradually, if intolerable side effects occurs switch to one less likely to cause the effect, attempt non- drug treatments, or symptomatic treatment

Use of antidepressants in and breastfeeding

 Decisions about treating depression during pregnancy should be made on an individual basis, taking into account the risks and benefits of the options available to the woman.  Involve the woman, and her family where appropriate, in all decisions about treatment. Discuss: - The risks of stopping antidepressants abruptly. - The risks associated with not treating depression during pregnancy. Explain that psychiatric illness during pregnancy is an independent risk factor for congenital malformation, preterm delivery, and perinatal mortality. - The possibility that there may still be a risk of malformations if a drug with known teratogenic risk is stopped as soon as pregnancy is confirmed. - The treatment options available to the woman (no intervention ['watchful waiting'], psychological treatment, antidepressant treatment, or a combination of psychological and antidepressant treatment).

If a patient is to remain on an antidepressant they should be referred to a psychiatrist, and support will be arranged. Before pregnancy: If mild or no symptoms for 6 months or longer, consider tapering and discontinuation before conception. This may not be appropriate if the depression is severe or recurrent. Refer to secondary care if the patient has suicidal or acute depression. Page 3 of 6 DepressionGUI201611V2 0FINAL

During pregnancy, and already taking antidepressants: Patients who want to stay on medication should discuss this with a psychiatrist and obstetrician. Those who want to discontinue can taper and stop if no symptoms occur. Women with recurrent depression, with or without antidepressants, may be helped by psychological therapies instead or as well. Women with severe depression (e.g. weight loss, suicidal attempts) should remain on antidepressants.

During pregnancy, not taking antidepressants , or careful choice of antidepressant where symptoms are moderate to severe – seek specialist advice.

Psychosis All pregnant women with a history or indications of depression should be advised to seek psychiatric help urgently if psychotic symptoms develop.

Stopping antidepressant treatment – refer to Appendix 1 table swapping and stopping advice

 patients should be advised not to stop treatment suddenly or omit doses - patients should also be forewarned about possible symptoms that may occur when treatment is discontinued  Drug and Therapeutics Bulletin advises: o after a 'standard' 6-8 months treatment it is recommended that treatment should be tapered off over a 6-8 week period o if the patient has been on maintenance therapy then an even more gradual tapering e.g. by 25%- 50% of the treatment dose every 4-6 weeks, is advised o if a treatment course has lasted less than 8 weeks then discontinuation over 1-2 weeks is considered safe.

Discontinuation symptoms

Discontinuation symptoms can be avoided by slow tapering of dose as described above. If discontinuation symptoms occur then the rate of drug withdrawal should be slowed or (if the drug has been stopped) the patient should be given reassurance that symptoms rarely last more than 1-2 weeks.

. advise people that discontinuation symptoms may occur on stopping, missing doses or, occasionally, reducing the dose of the drug. Explain that these are usually mild and self- limiting over about 1 week, but can be severe, particularly if the drug is stopped abruptly . advise the person to see their practitioner if they experience significant discontinuation symptoms. If symptoms occur: . monitor them and reassure the person if symptoms are mild . consider reintroducing the original antidepressant at the dose that was effective (or another antidepressant with a longer half-life from the same class) if symptoms are severe, and reduce the dose gradually while monitoring symptoms . for detailed guidance then consult the full NICE guideline (See references).

Swapping antidepressant treatment - refer to Appendix 1 table swapping and stopping advice

When swapping from one antidepressant to another, abrupt withdrawal should be avoided. Cross-tapering is preferred, where the dose of the ineffective or poorly tolerated drug is slowly reduced while the new drug is slowly introduced for example:

week 1 week 2 week 3 week 4 withdrawing 150 mg od 100mg od 50 mg od 25 mg od Nil introducing citalopram Nil 10 mg od 10mg od 20 mg od 20 mg od Page 4 of 6 DepressionGUI201611V2 0FINAL

Appendix 1 - Anti-depressant use: swapping and stopping The table below has been adapted from the Maudsley prescribing guidelines. There are no clear guidelines on switching antidepressants, so caution is required. Also the specific summary of product characteristics for each of the antidepressants involved should be consulted. To Tricyclic Citalopram Sertraline Fluoxetine Mirtazapine Antidepressants Venlafaxine From (TCA)

Withdraw citalopram. Withdraw Withdraw. Cross taper cautiously Citalopram Start sertraline at Start Fluoxetine at Start Paroxetine at Cross taper cautiously Cross taper cautiously 37.5mg OM 25mg per day 10mg OM 10mg OM Increase very slowly

Withdraw then start Withdraw then start Cross taper cautiously Withdraw sertraline then Withdraw then start Citalopram 10mg per Paroxetine 10mg per Cross taper cautiously with very low dose of start venlafaxine 37.5mg per Sertraline Fluoxetine day day TCA day Stop fluoxetine. Stop fluoxetine. Stop fluoxetine. Stop Fluoxetine. Withdraw. Wait 4-7 days. Start Wait 4-7 days. Start Cross-taper cautiously, Wait 4-7 days. Start Wait 4-7 days. Start TCA Start venlafaxine 37.5mg citalopram at 10mg sertraline at 25mg per start mirtazapine at Fluoxetine paroxetine at 10mg OM at very low dose. OM OM and increase day and increase 15mg ON and increase slowly Increase dose slowly. Increase very slowly. slowly slowly

Withdraw paroxetine Withdraw paroxetine. Cross taper cautiously Cross taper cautiously. Withdraw paroxetine. Start citalopram 10mg Start sertraline at Cross taper cautiously with very low dose of Start venlafaxine 37.5mg Paroxetine Start Fluoxetine per day 25mg per day TCA OM. Increase very slowly

Cautious cross tapering. Cross taper Cross taper Cross taper Cross taper cautiously Start TCA using very low Cross taper cautiously Mirtazapine cautiously cautiously cautiously starting dose

Halve dose. Halve dose. Halve dose. Halve dose. Cross taper cautiously, TCA Add Citalopram then Add Sertraline then Add Fluoxetine then Add Paroxetine then Cross taper cautiously Cross taper cautiously starting venlafaxine slowly withdraw TCA slowly withdraw TCA slowly withdraw TCA slowly withdraw TCA 37.5mg OM

Cross taper Cross taper Cross taper Cross taper Cautious cross tapering. cautiously. Start with cautiously. Start cautiously. Start cautiously. Start with Venlafaxine Cross taper cautiously Start TCA using very low citalopram 10mg per with sertraline with 20mg fluoxetine paroxetine 10mg per starting dose day 25mg per day on alternate days. day

Reduce over at least 4 Reduce by Reduce Reduce weeks. Use liquid if Reduce over at Reduce 20mg per 2 weeks to Reduce over 4 weeks Stopping over 4 weeks over 4 weeks necessary, reducing least 4 weeks over 4 weeks 20mg/day then stop. 1mg/week or more.

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Title Guidance for the treatment of depression in adults Document reference DepressionGUI201611V2 0FINAL References NICE Depression in adults: recognition and management Clinical guideline [CG90] Last updated: April 2016 https://www.nice.org.uk/guidance/cg90?unlid=7710146562016519212417

NICE Clinical knowledge summaries: Depression last revised October 2015. http://cks.nice.org.uk/depression

NICE Clinical knowledge summaries: Depression – antenatal and postnatal Last revised September 2015 http://cks.nice.org.uk/depression- antenatal-and-postnatal

GP notebook http://www.gpnotebook.co.uk/simplepage.cfm?ID=1637482568

MHRA bulletin – SSRIs and QT prolongation Last modified: 17th February 2015 http://www.mhra.gov.uk/ssri-learning- module/con146583?usesecondary=&showpage=20

UKMI Q&A Antidepressants in coronary heart disease September 2016 https://www.sps.nhs.uk/articles/what-is-the-antidepressant-of-choice- in-coronary-heart-disease-chd/

Vortioxetine for treating major depressive episodes Technology appraisal guidance [TA367] Published date: 25 November 2015 https://www.nice.org.uk/guidance/ta367?unlid=539223797201642482826

Author Natalie Prior, Senior Pharmacist MECCG Consulted with Dr Sam Bhima, GPwSI substance misuse & Clinical Lead (mental health) MECCG Approved by MMC Date approved October 2016 Date review October 2018

Previous version Key changes January 2012 Flow chart updated to include doses and liothyronine removed New addition to formulary Vortioxetine

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