Citalopram dose reduction flow chart based on advice from the mhra – november 201
NHS Bristol NHS North Somerset NHS South Gloucestershire Citalopram and escitalopram dose reduction flow chart based on advice from the MHRA – November 2011 If citalopram or escitalopram dose is currently above the new Citalopram or escitalopram maximum dose – Prescriber consider to offer an appointment to discuss with is taken with other
service user / patient. Document discussion to reduce dose, stay on current dose
medicines that also prolong the QT interval MHRA guidance 2011 Elderly or reduced hepatic Known to need more than Adult citalopram function – reduce dose to a recommended new dose – e.g. dose above 40mg daily –
The maximum dose of Citalopram is now 40mg daily in adults (not licensed in
children). In the elderly (65 years and older) and those with reduced hepatic function the maximum dose is lowered to 20mg daily. For escitalopram the
Use of citalopram or escitalopram with other medicinal products known to prolong
Use of citalopram and escitalopram is contraindicated in patients with a known
If all other options are exhausted consider above
those at increased risk of Torsades de Pointes.
Version 5 - Author – T.Turner for AWP Medicines Management Group in collaboration with local PCT Medicines Management Team – ref-Stockley drug interactions [medicinescomplete.com], Maudsley prescribing guidelines 10th edition, Bazire et al-citalopram maximum dose reductions flow chart, medicines information bulletin- Oxford health NHS foundation Trust, SPC of relevant products [emc.medicines.org.uk], AWP databank search Nov 2011. Tips for applying the guidance The service user/patient should be seen by their prescriber to discuss the guidance and options or need for treatment change. The prescriber should carry out any changes and then monitor the person as for any other change in antidepressant treatment. Where the prescriber is a GP their local psychiatrist or mental health pharmacist can give advice. Alternatively clinical advice can be obtained by emailingwhere a member of the pharmacy team wil pick up the enquiry. Where above new license doses are needed then document rationale, capacity and consent and monitor with ECG every 6-12 months. For depression there does not appear to be a dose – response curve, so higher doses are usual y not effective. This is different to other conditions such as OCD or PTSD. Risk factors for prolonged QTc interval Hypomagnesia, hypokalaemia, hypocalcaemia, bradycardia (including drug induced, digoxin, beta -blockers etc), congenital prolonged QTc interval, underlying cardiomyopathy, cytochrome P450 inhibitors, long term alcohol use, female gender, thyroid disease. Anorexia nervosa can be a risk factor as electrolyte imbalance more likely. Medicines that prolong the QT interval (not exhaustive) Antibiotics – azithromycin, erythromycin, clarithromycin, ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, metronidazole (with alcohol) - Antifungals – ketoconazole, fluconazole (with alcohol) Antivirals – Nelfinavir Antiarrhythmics – disopyramide, procainamide, quinidine, amiodarone, dronedarone, sotalol. Antidepressants – tricyclics (dose related), trazadone, venlafaxine. Antipsychotics – Higher risk- haloperidol, pimozide, Medium risk -amisulpride, chlorpromazine, Quetiapine, sulpiride, Lower risk – aripiprazole, paliperidone, clozapine, flupentixol, fluphenazine, perphenazine, prochlorperazine, olanzapine, risperidone. Antimalarials – chloroquine, mefloquine Others – methadone (especial y above 100mg daily) Lithium (if levels raised), quinine (at higher doses). Switching antidepressants What to switch to – (see formulary for local choices) SSRIs such as fluoxetine or sertraline (variety of licensed indications, check drug interactions), paroxetine (in NICE guidance for PTSD), mirtazapine (licensed for depression). How to switch – there is no single method which is best – drop, cross taper and stop method – drop dose citalopram, add new antidepressant and taper off citalopram. Watch for serotonin syndrome and citalopram withdrawal – a straight switch – swap another antidepressant for citalopram at an equivalent dose. Watch for signs of serotonin syndrome and citalopram withdrawal – a drop, stop and then switch – lower dose of citalopram and then stop, once citalopram stopped then start new antidepressant. Watch for withdrawal symptoms and deterioration of mental health. Serotonin syndrome symptoms Agitation, restlessness, anxiety, confusion, shivering, tremor, in-coordination, nausea, diarrhoea, tachycardia, hypertension, hyperflexia SSRI withdrawal symptoms – irritability, anxiety, sleep disturbance, fatigue, dizziness, tremor, electronic shock sensations, sweating, nausea, diarrhoea, numbness, ataxia
A single ECG reading is not necessarily diagnostic of absence of QT prolongation as this wil vary from day to day. Therefore fol ow-up ECGs may be useful where there are risk factors. A QTc interval of below 450msecs is usual y considered safe, 450-500msec is considered to be done with caution with regular monitoring and try to reduce modifiable risk factors. Above 500 msecs take steps to reduce risk factors and change treatment, above 600msecs; seek specialist advice.
QT values of the SSRIs – QT values in a study (Isbister 2004) were – citalopram 250msec, fluoxetine 432 msec, Sertraline 429 msec, non-cardiac effect drugs 423 msec. (ICH guidelines suggest a prolongation of>10msec to be of regulatory concern) Escitalopram QTc prolongation is 4.3 msec at 10mg daily and 10.7 msec at 30mg daily.
L’adolescent entre psyché et soma lescent comme une tentative d’aménagerL’ part d’entre nous la véritable ren- ce nouvel espace familial ; et ceci du faittion du statut de celui-ci et de son appar-tenance. Jusqu’alors en effet, aussi essen-parricidaire avec les parents, qu’introduitl’organisation de la personnalité, le corpsmiliarisation est nécessaire pour intégrerfa