Central Nervous System Drugs used for the treatment of depression Anxiolytics and hypnotics Drugs used in psychosis and related disorders Drugs used in substance dependence for patients with established chemical dependence Drugs used for the treatment of dementia Drugs used for the treatment of obesity Drugs used for the treatment of nausea and vertigo Drugs used for the treatment of Parkinson s disease and related disorders Drugs used for the treatment of epilepsy Updated: 18.08.2010
Drugs used for the treatment of depression Selective Serotonin Reuptake Inhibitors Tricyclic and related antidepressants Others antidepressants Back to main Index
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. CSM: Hyponatraemia should be considered in all patients who develop drowsiness, confusion, or convulsions whilst taking an antidepressant. Suicidal behaviour and antidepressant therapy The use of antidepressants has been linked with suicidal thoughts and behaviour. Where necessary patients should be monitored for suicidal behaviour, self-harm, or hostility, particularly at the beginning of treatment or if the dose is changed. In case of needing to treat patients with suicidal ideation, SSRIs as a class are the safest option in overdose. Tricyclic antidepressants, monoamine-oxidase inhibitors (MAOI) and venlafaxine carry most risk of death in overdose. SSRIs and bleeding SSRIs are associated with an increased risk of bleeding, especially in older people or in people taking other drugs that have the potential to damage the gastrointestinal mucosa or interfere with clotting. Consider alternative antidepressants and/or prescribing a gastroprotective drug in older people who are taking non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin. Do not normally offer SSRIs to patients taking oral or parenteral anticoagulants consider mirtazepine instead, although INR may rise slightly even with mirtazepine. CSM summary guidance on SSRIs Use the lowest possible dose Monitor closely in early stages for restlessness, agitation and suicidality, particularly in those aged 30 or less Doses should be tapered gradually on stopping Venlafaxine is as dangerous in overdose as some tricyclic antidepressants Prescribing of St. John s Wort (Hypericum perforatum) St. John s Wort is a popular unlicensed herbal remedy for treating mild depression. However, preparations of St John s Wort can induce drug metabolising enzymes and a number of important interactions with conventional drugs have been identified, see current BNF. The amount of active ingredient can vary between different preparations of St John s Wort and switching from one to another can change the degree of enzyme induction. Furthermore, when a patient stops taking St John s Wort, concentrations of interacting drugs may increase, leading to toxicity. Antidepressants should not be used with St John's Wort because of the potential for interaction. Minimum effective doses (MED) Inadequate dosing may account for up to 20% of treatment failures. It is important to use doses that are sufficiently high for effective treatment, but not so high to cause toxic effects. Lower doses should be used for the initial treatment of the elderly. The minimum effective dose (MED) of each drug appears in the Formulation column. Sequencing treatments after inadequate response - Switching and combining antidepressants
When reviewing treatment after an inadequate response to initial pharmacological interventions: check adherence to, and side effects from, initial treatment increase the frequency of appointments be aware that using a single antidepressant is usually associated with a lower side-effect burden consider reintroducing treatments that have been inadequately delivered or adhered to, including increasing the dose or switching antidepressants. When switching antidepressants, consider: initially, a different SSRI or a better tolerated newer-generation antidepressant subsequently, an antidepressant of a different class that may be less well tolerated (such as venlafaxine, a TCA or an MAOI). Do not switch to, or start, dosulepin. For information on combining and augmenting antidepressants see section on Combining and augmenting medication The Mental Health National Service Framework outlines recent policy and consultation documents, implementation guides and good practice examples of mental health services. For more information visit the Department of Health website: http://www.dh.gov.uk/en/healthcare/nationalserviceframeworks/index.htm
Drugs used for the treatment of depression index Selective Serotonin Reuptake inhibitors Interactions of SSRIs with other medications Medication for chronic physical health problem Recommendation Non-steroidal anti-inflammatory drugs (NSAIDs) Warfarin or heparin Aspirin Triptan drugs for migraine Monoamine oxidase B inhibitors (for example,selegiline and rasagiline) Theophylline, clozapine, methadone or tizamidine Flecainide or propafenone Atomoxetine Do not normally offer SSRIs but if no suitable alternatives can be identified, offer gastroprotective medicines (for example, proton pump inhibitors) together with the SSRI Consider mirtazapine, mianserin, moclobemide, reboxetine or trazodone Do not normally offer SSRIs Consider mirtazapine (note that when taken with warfarin, the international normalised ratio [INR] may increase slightly) Use SSRIs with caution if no suitable alternatives can be identified, offer gastroprotective medicines together with the SSRI Consider trazodone, mianserin or reboxetine when aspirin is used as a single agent Consider mirtazapine Do not offer SSRIs Offer mirtazapine, trazodone, mianserin or reboxetine Do not normally offer SSRIs Offer mirtazapine, trazodone, mianserin or reboxetine Do not normally offer fluvoxamine Offer sertraline or citalopram Offer sertraline as the preferred antidepressant Mirtazapine and moclobemide may also be used Do not offer fluoxetine or paroxetine Offer a different SSRI
Has least number of interactions reported amongst all SSRIs. Citalopram Depressive illness, panic disorder Tablets, oral drops MED: 20mg/day Dosage adjustment is not necessary in cases of mild or moderate renal impairment. No information is available in cases of severe renal impairment (creatinine clearance <20 ml / min). Suggested option in mild moderate renal and hepatic impairment start with a dose of 10mg/day and titrate slowly if necessary. SSRIs are considered the first line antidepressant option in patients with epilepsy; citalopram may be considered as one of the safest options due to its lack of interactions with anticonvulsants. Sertraline Fluoxetine Depressive illness, OCD, post-traumatic stress disorder (PTSD) in women Major depression; bulimia nervosa, obsessive compulsive disorder (OCD) Tablets MED: 50mg/day Capsules, Liquid MED: 20mg/day 8mg (4 drops) = 10mg tablets Safety and efficacy has been shown for depression post myocardial infarction and for the treatment of depression in diabetes. Sertraline may also be considered as one of the safest options in patients with epilepsy due to its lack of interactions with anticonvulsants. Fluoxetine is associated with a higher risk of drug interactions than citalopram and sertraline. Consider the possible small risk of congenital cardiac defects, which is similar to that of paroxetine in the context of the benefits of treating depression in pregnancy. Efficacy established for licensed indications and also for the unlicensed indication of maintenance treatment of depression. Not useful if a degree of sedation is required. Paroxetine Major depression, OCD, panic disorder, social anxiety disorder, PTSD, generalized anxiety disorder Tablets, Oral suspension MED: 20mg/day Active metabolite has a long ½ life (7-9 days). Wide range of interactions reported As paroxetine is associated with more discontinuation symptoms than any other SSRI, it is not recommended as a first line antidepressant. Paroxetine is associated with a higher risk of drug interactions than citalopram and sertraline CSM: Paroxetine should only be used at the dose of 20mg/day for the treatment of depression. There is no evidence from clinical trials that increasing the dose above recommended dose increases efficacy. Extrapyramidal reactions (including orofacial dystonias) and withdrawal syndrome are reported to the CSM more commonly with paroxetine than with other SSRIs.
Escitalopram All SSRIs in children and adolescents ELFT: Reviewed in December 2009 and considered as a non-formulary drug. This decision extends to its use in anxiety disorders CSM: The balance of risks and benefits for the treatment of depressive illness in individuals under 18 years is considered unfavourable for the SSRIs citalopram, escitalopram, paroxetine, and sertraline, and for mirtazapine and venlafaxine. Clinical trials have failed to show efficacy and have shown an increase in harmful outcomes. However, it is recognised that specialists may sometimes decide to use these drugs. Children and adolescents should be monitored carefully for suicidal behaviour, selfharm or hostility, particularly at the beginning of treatment. Drugs used for the treatment of depression index Tricyclic and related antidepressants
Lofepramine Depression Tablets, oral suspension MED:140mg/day Amitriptyline Clomipramine Imipramine Trazodone Dosulepin Depression Depression, phobic and obsessional states Depression Depression, anxiety Depressive illness Tablets, oral solution MED: 75mg/day Capsules, MR tablets MED: 75mg/day Tablets MED: 75mg/day Tablets, capsules, sugar free liquid MED: 150mg/day Tablets MED: 75mg/day Toxicity of tricyclic and related antidepressants in overdose relative to SSRIs Drug Toxicity Dosulepin Most Toxic Amitriptyline Imipramine Less sedating, lower incidence of antimuscarinic effects and less dangerous in overdose. Recommended TCA for the elderly. Dangerous in overdose and arrhythmogenic. It is important to exercise caution when prescribing especially at doses higher than 50mg/day. Avoid in the elderly and patients with arrhythmias and CVD Avoid prescribing for patients with suicidal ideation Consider prescribing smaller quantities when possible. Not recommended by BNF for the treatment of depression. Useful when sedation required. Much less toxic in overdose compared to dosulepine, amitriptyline and imipramine. Less sedating than amitriptyline women however have poor tolerance to imipramine. More toxic than clomipramine in overdose. Trazodone is recommended particularly where sedation is required. NICE + MHRA: Dosulepin has a small margin of safety between the (maximum) therapeutic dose and potentially fatal doses. Guidance advises that dosulepin should only be initiated by specialist mental health practitioners (including GP s with a specialist interest in mental health). Evidence supporting its tolerability relative to other antidepressants is outweighed by the cardiac risk and toxicity in overdose. Patients currently prescribed dosulepin should be reviewed especially if they suffer from cardiovascular disease. Do not switch to, or start, dosulepin because evidence supporting its tolerability relative to other antidepressants is outweighed by the increased cardiac risk and toxicity in overdose.
Clomipramine Trazodone Lofepramine Least Toxic Drugs used for the treatment of depression index Others antidepressants
Before prescribing practitioners should take into account its propensity to cause sedation and weight gain. Mirtazepine Major depression Tablets, oral solution MED: 30mg/day Blood disorders Patients should be advised to report any fever, sore throat, stomatitis or other signs of infection during treatment. Blood count should be performed and the drug stopped immediately if blood dyscrasia suspected Mianserine Moclobemide Reboxetine Venlafaxine Depressive illness, particularly where sedation is required Depressive illness; social anxiety disorder Major depression Major depression, generalised anxiety disorder Tablets Tablets MED: 300mg/day Tablets MED: 8mg/day MR Capsules, Tablets MED:75mg/day Withdrawal Nausea, vomiting, dizziness, agitation, anxiety, and headache are most common features of withdrawal if treatment stopped abruptly or if dose reduced markedly; dose should be reduced over several weeks A full blood count is recommended every 4 weeks during the first 3 months of treatment; clinical monitoring should continue subsequently and treatment should be stopped and full blood count obtained if fever, sore throat, stomatitis, or other signs of infection develop NB. This is hardly ever used locally Beware of the need to wash out previous antidepressant before prescribing. See current BNF for more information. Moclobemide is less likely to interact with foods and drugs, and is associated with a low incidence of seizures in patients with depression compared to MAOIs. It is considered a good choice in patients with epilepsy and is not cautioned or contraindicated in these patients. Monitor carefully as there is a relative lack of data on side effects. Venlafaxine is a serotonin/noradrenergic/dopaminergic reuptake inhibitor (SNDRI) and is not recommended as a first line agent for depression. It has been shown to have similar seizure rates in overdose to dosulepin (dothiepin) and has a higher risk of discontinuation symptoms than most SSRIs. At low doses (<150mg/day) it is no more effective than SSRIs as noradrenergic activity is exerted only at doses above 150mg/day. At doses above 150mg/day there is some evidence that it is more effective than SSRIs however it has been shown to cause increases in blood pressure. Venlafaxine also causes significantly higher gastrointestinal problems than
fluoxetine at both low and high doses. It is important to increase the dose gradually as there is otherwise a greater likelihood of person stopping treatment due to side effects. There is an increased likelihood of discontinuation It is associated with a greater risk of death from overdose compared to other antidepressants used in primary care Regular blood pressure monitoring (at least 6 monthly) is recommended. Doses of venlafaxine 300mg/day should only be prescribed under the supervision or advice of a specialist mental health medical practitioner. Venlafaxine should not be prescribed for patients with pre-existing heart disease. Any such patients currently prescribed it should be reviewed. Sertraline is the only SSRI with evidence of use in patients with CHD. Withdrawal Gastro-intestinal disturbances, headache, anxiety, dizziness, paraesthesia, tremor, sleep disturbances, and sweating are most common features of withdrawal if treatment stopped abruptly or if dose reduced markedly; dose should be reduced over several weeks. Duloxetine [Cymbalta ] Aomelatine [Valdoxan ] Major depressive disorder Capsules MED: 60mg/day (start treatment with 30mg dose daily) This is another SNRI that has been licensed for depression. ELFT: Duloxetine may be initiated by specialists. There is no evidence that it is any better than SSRIs and hence not recommended for 1 st line use. It is important to increase the dose gradually as there is otherwise a greater likelihood of person stopping treatment due to side effects. Monitor BP regularly as duloxetine has the potential for exacerbating hypertension ELFT: The use of agomelatine (Valdoxan ) is not approved for the treatment of depressive episodes in adults. It is a non-formulary drug, restricted to specialist consultant psychiatrist for patients who have not responded to other established antidepressants. GP would not be expected to prescribe it in primary care therefore any requests for GPs to prescribe should be declined and referred back to the trust.
Drugs used for the treatment of depression index Combining and augmenting medication Augmentation is when an antidepressant is used with a non-antidepressant drug and combination is when two antidepressants are used together. When using combinations of medications (To be initiated in primary care only in consultation with a consultant psychiatrist): select medications that are known to be safe when used together be aware of the increased side-effect burden this usually causes discuss the rationale for any combination with the person with depression, follow GMC guidance if off-label medication is prescribed, and monitor carefully for adverse effects be familiar with primary evidence and consider obtaining a second opinion when using unusual combinations, the evidence for the efficacy of a chosen strategy is limited or the risk benefit ratio is unclear document the rationale for the chosen combination ensure that the person with depression is informed about, and prepared to tolerate, the increased side-effect burden Drug Notes on prescribing Lithium augmentation When prescribing lithium: monitor renal and thyroid function before treatment and every 6 months during treatment (more often if there is evidence of renal impairment) consider ECG monitoring in people with depression who are at high risk of cardiovascular disease monitor serum lithium levels 1 week after initiation and each dose change until stable, and every 3 months thereafter. perform an annual health and weight/bmi check documented in medical record document date for the next monitoring tests lithium record book/medical records prescriptions should have specific dosage instruction. ( As required or directed is not acceptable) prescribed by brand name When prescribing an antipsychotic, monitor weight, lipid and glucose levels, and side effects (for example, extrapyramidal side effects and prolactin-related side effects with risperidone). Antipsychotic augmentation Combination monitor weight with mirtazepine The following strategies should not be used routinely: augmentation of an antidepressant with a benzodiazepine for more than 2 weeks as there is a risk of dependence augmentation of an antidepressant with buspirone, carbamazepine, lamotrigine or valproate as there is insufficient evidence for their use augmentation of an antidepressant with pindolol or thyroid hormones as there is inconsistent evidence of effectiveness
References: Joint Formulary Committee. British National Formulary. 54 th Ed. London: British Medical Association and Royal Pharmaceutical Society of Great Britain. 2007. National Institute for Health and Clinical Excellence. Depression: management of depression in primary and secondary care Clinical Guidance 23. December 2004. Available from: www.nice.org.uk. Accessed 17/03/08 National Institute for Health and Clinical Excellence. NICE amends depression and anxiety guidance in line with safety recommendations. 2007/022. Available from www.nice.org.uk. Accessed 17/03/08 Taylor D, Panton C, Kerwin. The Maudsley Prescribing Guidelines, 9th edition. 2007. Informa Healthcare Ltd. Buckley NA, McManus PR. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom, mortality data BMJ. 2002;325:1332-1333 Clinical Knowledge Summaries. Depression 2003. SCHIN Ltd, Centre for Health Informatics at Newcastle. Available from: http://www.cks.library.nhs.uk/depression. Accessed 16/02/08. NPC. Depression: The management of depression in primary care. MeReC Briefing.2005/2006; Issue. No. 31. Summary of Product Characteristics. citalopram, fluoxetine, sertraline, paroxetine, escitalopram, lofepramine, amitriptyline, clomipramine, imipramine, trazodone, mirtazepine, dosulepine, venlafaxine, moclobemide, reboxetine, duloxetine. Available from: www.medicines.org.uk. Accessed 16/02/08. MHRA. Antidepressants and risk of suicidal behaviour. Drug Safety Update: Volume 1, Issue 1, August 2007 MHRA. Dosulepin: measures to reduce risk of fatal overdose. Drug Safety Update: Volume 1, Issue 5, December 2007 National Service Framework. Mental Health. London: Department of Health. 1999. Available from: www.dh.gov.uk. Accessed 16/02/08. Armstrong A, Bishop S, Radhamanohar M. Medication and Risk of Falls in the Older Person. Approved: March 2006. http://10.148.22.36:8080/thpct/prescribing/practice%20tools%20documents/medication%20and%20the%20risk%20of%20falls%20in%20the%20older%20person. pdf New NICE Guidelines on drugs used in schizophrenia NICE/SCIE guideline on dementia Banerjee S. The use of antipsychotic medication for people with dementia: time for action. A report for the Minister of State for Care Services. November 2009 Drugs used for the treatment of depression index Back to main Index Anxiolytics and hypnotics Anxiolytics short term management Anxiolytics long term treatment Hypnotics Anxiolytics short-term management
Anxiolytics should be used for the immediate short term management of generalised anxiety disorder only. They are not recommended for the treatment of Panic Disorder. Prescribing of these drugs can cause dependence (both physical and psychological) and tolerance and thus should not be used for more than 2-4 weeks and only after causal factors are known. CSM: Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety that is severe, disabling or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic, or psychotic illness. The use of benzodiazepines to treat short-term mild anxiety is inappropriate and unsuitable. Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or subjecting the individual to extreme distress. The Mental Health National Service Framework outlines recent policy and consultation documents, implementation guides and good practice examples of mental health services. For more information visit the Department of Health website: http://www.dh.gov.uk/en/healthcare/nationalserviceframeworks/index.htm Hydroxyzine Short term management of anxiety Tablets NICE recommends sedating antihistamines as an option for immediate management of anxiety. Diazepam Tablets, Short term management of liquid Lorazepam anxiety Tablets, S/L tablets Consider in the elderly and those with liver disease. Barbiturates are not recommended as they have more side-effects, interactions and are more dangerous in overdose. Anxiolytics long term treatment
SSRIs Generalised anxiety disorder, panic disorder Various See depression section and relevant SPCs for more details. Clomipramine Used unlicensed for anxiolytic effect. Useful when sedation is required. Depressive illness, phobic Capsules, Much less toxic in overdose compared to dosulepin, amitriptyline and and obsessional states MR tablets imipramine. Imipramine Venlafaxine Propranolol Depressive illness, nocturnal enuresis in children Generalised anxiety disorder Somatic symptoms of anxiety Anxiolytics and hypnotics index Hypnotics Tablets MR capsules Tablets Used unlicensed for anxiolytic effect. Less sedating than amitriptyline women however have poor tolerance to imipramine. More toxic than clomipramine in overdose. See depression section for more details. Care when treating patients with conduction problems / hypotension / bradycardia. Hypnotics should not be routinely prescribed and should be reserved for short courses in the acutely distressed only. Tolerance to their effects develops within 3 to 14 days of continuous use and long-term efficacy cannot be assured. NICE : Doctors should consider using non-medicine treatments, and then, if they think that a hypnotic medicine is the appropriate way to treat severe insomnia that is interfering with normal daily life, they should prescribe one for only short periods of time and strictly according to the licence for the drug. Because there is no firm evidence of differences in the effects of zaleplon, zolpidem, zopiclone and the shorter-acting benzodiazepines, NICE recommends that doctors should prescribe the cheapest drug, taking into account the daily dose required and the cost for each dose. Treatment should only be changed from one of these hypnotics to another if side effects occur that are directly related to the medicine. If treatment with one of these hypnotic medicines does not work, the doctor should not prescribe one of the others. CSM: Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety that is severe, disabling or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic, or psychotic illness. The use of benzodiazepines to treat short-term mild anxiety is inappropriate and unsuitable. Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or subjecting the individual to extreme distress.
Promethazine Night sedation and insomnia (short term) Tablet, elixir However, used first line by ELFT Temazepam Insomnia (short term) Tablets Not to be used for more than 2 weeks. Zopiclone Insomnia (short term) Tablets Zopiclone is not free from withdrawal problems. Has a short half life with potential to cause residual effects. Not to be used for more than 2 weeks. References: Joint Formulary Committee. British National Formulary. 54 th Ed. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2007. National Institute for Clinical Excellence. Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia. Technology Appraisal 77; April 2004. Available from: www.nice.org.uk. Accessed 17/03/08. National Institute for Clinical Excellence. Anxiety: management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care. Clinical Guideline 22; December 2004. Available from: www.nice.org.uk. Accessed 16/02/08. Summary of Product Characteristics. hydroxyzine, diazepam, lorazaepam, clomipramine, Imipramine, venlafaxine, propranolol. Available from: www.medicines.org.uk.accessed 16/02/08. Department of Health. Patient Safety: Benzodiazepines warning. CMO's update 37; January 2004. Clinical Knowledge Summaries. Anxiety. SCHIN Ltd, Centre for Health Informatics at Newcastle. Available from: http://www.cks.library.nhs.uk. Accessed 16/02/08. NPC. Benzodiazepines and newer hypnotics. MeReC Bulletin. No. 5. 2004/2005. Taylor D, Panton C, Kerwin. The Maudsley Prescribing Guidelines. 9th edition. 2007. Informa Healthcare Ltd. National Service Framework. Mental Health. London: Department of Health.1999. Available from: www.dh.gov.uk. Accessed 16/02/08. MHRA. Lorazepam: reduction of recommended maximum daily dose. Drug Safety Update: Volume 1, Issue 3, October 2007. Available from: http://www.mhra.gov.uk/publications/safetyguidance/drugsafetyupdate/con2032518 Accessed 16/02/08 Armstrong A, Bishop S, Radhamanohar M. Medication and Risk of Falls in the Older Person. Approved: March 2006. http://10.148.22.36:8080/thpct/prescribing/practice%20tools%20documents/medication%20and%20the%20risk%20of%20falls%20in%20the%20older%20person. pdf Anxiolytics and hypnotics index Back to main Index Drugs used in psychosis and related disorders Antipsychotics first generation
Antipsychotics second generation Drugs used for Bipolar affective disorder - Lithium Drugs used for Bipolar affective disorder - Others
Liaise with specialist mental health services for all patients with psychiatric illnesses to co-ordinate continuing management Guidance on the prescribing of antipsychotics Prescribing of more than one antipsychotic at the same time is not recommended Advice on doses above the BNF upper limits from the Royal College of Psychiatrists see BNF Elderly are particularly susceptible to adverse effects including hypotension All first generation antipsychotics cause extrapyramidal side effects, sometimes necessitating the use of anticholinergic medication like procyclidine. Use with caution in elderly. NICE Guidelines: Schizophrenia Pharmacological interventions For people with newly diagnosed schizophrenia, offer oral antipsychotic medication. Provide information and discuss the benefits and sideeffect profile of each drug with the service user. The choice of drug should be made by the service user and healthcare professional together, considering: the relative potential of individual antipsychotic drugs to cause extrapyramidal side effects (including akathisia), metabolic side effects (including weight gain) and other side effects (including unpleasant subjective experiences) the views of the carer where the service user agrees. Do not initiate regular combined antipsychotic medication, except for short periods (for example, when changing medication). Interventions for people with schizophrenia whose illness has not responded adequately to treatment For people with schizophrenia whose illness has not responded adequately to pharmacological or psychological treatment: review the diagnosis establish that there has been adherence to antipsychotic medication, prescribed at an adequate dose and for the correct duration review engagement with and use of psychological treatments and ensure that these have been offered according to this guideline. If family intervention has been undertaken suggestcbt; if CBT has been undertaken suggest family intervention for people in close contact with their families consider other causes of non-response, such as comorbid substance misuse (including alcohol), the concurrent use of other prescribed medication or physical illness. Offer clozapine to people with schizophrenia whose illness has not responded adequately to treatment despite the sequential use of adequate doses of at least two different antipsychotic drugs. At least one of the drugs should be a non-clozapine second-generationantipsychotic. Antipsychotics and stroke Olanzapine and risperidone are associated with an increased risk of stroke in elderly patients with dementia CSM: Risperidone or olanzapine should not be used for treating behavioural symptoms of dementia For acute psychotic conditions in elderly patients with dementia, risperidone should be limited to short-term use under specialist advice Olanzapine is not licensed for acute psychoses
The possibility of cerebrovascular events should be considered carefully before treating any patient with a history of stroke or transient ischaemic attack Risk factors for cerebrovascular disease (e.g. hypertension, diabetes, smoking, and atrial fibrillation) should also be considered. Reducing the use of antipsychotic drugs in dementia Antipsychotic drugs should be prescribed only when a person is a risk to themselves or others, and where all other methods have been tried. This should be for a short period of three months only, while a care plan is put in place. Prescribers should note that risperidone is the only antipsychotic indicated for a behavioural problem in people with dementia, i.e. short-term treatment (up to six weeks) for persistent aggression in patients with moderate to severe Alzheimer s dementia. Healthcare professionals should follow the NICE/SCIE guideline on dementia for the management of non-cognitive symptoms and behaviour that challenges. The Mental Health National Service Framework outlines recent policy and consultation documents, implementation guides and good practice examples of mental health services. For more information visit the Department of Health website: http://www.dh.gov.uk/en/healthcare/nationalserviceframeworks/index.htm Drugs used in psychosis and related disorders index
Antipsychotics first generation Chlorpromazine Schizophrenia and other psychoses Haloperidol Trifluoperazine Sulpiride Zucolpentixole Schizophrenia and other psychoses Schizophrenia and other psychoses Schizophrenia Psychoses, particularly if agitated or aggressive behaviour Tablets, oral solution, suppositories Tablets, capsules, oral liquid Tablets, syrup, oral solution Tablets, oral solution Tablets Use 1 / 3 1 / 2 the adult dose in the elderly Avoid direct contact as risk of contact sensitisation Use ½ of adult dose in the elderly Long acting therefore lower doses are recommended in the elderly Trifluoperazine MR capsules (Spansules) no longer available Can cause hyperprolactinaemia which is linked firmly with sexual dysfunction, osteopenia, menstrual disturbances, gynacomastia, galactorrhoea and possibly with an increased risk of breast cancer. Antipsychotics second generation
Amisulpiride Aripiprazole [Abilify ] Olanzapine Schizophrenia Schizophrenia Schizophrenia, mania Tablets, solution Tablets, oral solution Tablets Most common side-effect is insomnia. Can also cause hyperprolactinaemia which may lead to sexual dysfunction, osteopenia, menstrual disturbances, gynacomastia, galactorrhoea. It may also be linked with an increased risk of breast cancer. Agitation is a recognized initial transient adverse effect. Concomitant benzodiazepine should be prescribed when initiating and during dose escalation. There is a need to monitor weight, plasma glucose and lipids at least yearly as olanzapine has a tendency to increase all, for which treatment may be necessary. Quetiapine increases cholesterol and triglycerides for which treatment may be necessary, yearly fasting lipid blood tests are indicated. Quetiapine is also associated with postural hypotension and thyroid function abnormalities. ELFT: Approved second line treatment for patients requiring treatment with quetiapine. Quetiapine Schizophrenia, mania, bipolar depression Tablets XL Tablets Patients considered suitable for Quetiapine XL are: Those at high risk of adverse effects to quetiapine (e.g. orthostatic hypotension) or those experiencing adverse effects that are related to peak concentrations on twice a day quetiapine (e.g. sedation and somnolence). Those requiring rapid titration. Patients where once a day dosing is beneficial e.g. patients who are chaotic with tablets or do not remember to take tablets. Please note; Quetiapine XL is not suitable for actively non-compliant patients. The modified release nature of the drug is completely dependent upon the tablet being swallowed whole. If tablets need to be crushed, then the standard release formulation and dosing schedule should be used. Patients stable and compliant with quetiapine twice a day regimes should NOT be switched to the XL preparation. Click here for ELFT guidelines on the use of quetiapine XL Risperidone Psychoses, mania Tablets, liquid Can cause hyperprolactinaemia which may lead to sexual dysfunction, osteopenia, menstrual disturbances, gynacomastia, galactorrhoea. It may also be linked with an increased risk of breast cancer. Clozapine Tower Hamlets Clozapine Clinic initiates and continues the prescribing of clozapine - 07967613924 Sertindole Initiation and continuation by secondary care only as part of a clinical study
Paliperidone [ Invega ] ELFT: A metabolite of risperidone, it is not recommended for prescribing in primary or secondary care Drugs used in psychosis and related disorders index Drugs used for Bipolar affective disorder - Lithium
Prescribe lithium salts by brand only as they have different bioavailabilities. When changing preparations, extra vigilance is required in monitoring for efficacy and toxicity. Lithium carbonate Lithium citrate Treatment and prophylaxis of mania, bipolar disorder, and recurrent depression, aggressive or selfmutilating behaviour MR tablets Liquid TDM: GPs are required to have the result at least yearly (clinical recommendation is 3 monthly). Target serum concentration: 0.4 1 mmol/litre. Sample time: 12 hours post dose. Notes: Sample needed on days 4 7 of treatment, and then every week until dosage has remained constant for 4 weeks and every 3 months thereafter. Doses are initially divided throughout the day, but once daily administration is preferred when lithium concentration has stabilised. See BNF for equivalence data as different products have different bioavailabilities. MR preparations are preferred over others due to its better pharmacokinetic profile. Lithium Citrate should be given in 2 divided doses. Lithium toxicity can be fatal. See BNF for symptoms. Lithium toxicity is made worse by sodium depletion. Care when prescribing with NSAIDs, ACEIs and diuretics all increase plasma lithium concentration. Lithium cards A lithium treatment card available from pharmacies tells patients how to take lithium preparations, what to do if a dose is missed, and what side-effects to expect. It also explains why regular blood tests are important and warns that some medicines and illnesses can change serum-lithium concentration. Cards may be purchased from the National Pharmacy Association. Tel: (01727) 858 687, email: sales@npa.co.uk. Drugs used in psychosis and related disorders index Drugs used for Bipolar affective disorder - Others
Semi-sodium valproate [Depakote ] is used by ELFT, however prior to discharge; patients will be switched over to sodium valproate MR for use in primary care. Warn patients it commonly causes weight gain & give advice on how to reduce this. Sodium valproate Treatment and prophylaxis of bipolar disorder (unlicensed) MR tablets, EC tablets TDM: Levels only required if toxicity or non-concordance is suspected. Target serum concentration: 50-100mg/L (350 700mmol/l) Sample time: Trough i.e. pre-dose Notes: Time to steady state 2-4 days. If levels are outside the therapeutic range, please assess patient concordance and contact the specialist for advice. M/R preparations Different preparations may vary in bioavailability; to avoid reduced effect or excessive side effects, it may be prudent to avoid changing the formulation. (The use of M/R tablets significantly lessens the incidence of dose-related side effects). CSM: See current BNF for symptoms of blood, hepatic or skin effects that the patient needs to be aware of and report. Carbamazepine Prophylaxis of bipolar disorder unresponsive to lithium tablets, MR tablets liquid, suppositories Carbamazepine is a potent CYP450 enzyme inducer, as well as an auto inducer care should be exercised when prescribing concomitantly with other drugs especially those with narrow therapeutic indices (e.g. theophylline). The risk of hyponatraemia may be increased when prescribing with other drugs that deplete sodium (e.g. diuretics). TDM: Levels only required if toxicity or non-concordance is suspected. Target serum concentration: 4-12 mg / L Sample time: Trough i.e. pre-dose Notes: Time to steady state is 2-4 weeks while therapy is initiated, 4 days with chronic therapy. If levels are outside the therapeutic range, please assess patient concordance and contact the specialist for advice. M/R preparations Different preparations may vary in bioavailability; to avoid reduced effect or excessive side effects, it may be prudent to avoid changing the formulation. (The use of M/R tablets significantly lessens the incidence of dose-related side effects).
References: Joint Formulary Committee. British National Formulary. 54th Ed. London: British Medical Association and Royal Pharmaceutical Society of Great Britain. 2007. National Institute for Clinical Excellence. Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care. Clinical Guideline 1. 2002. Available from: www.nice.org.uk. Accessed 7/02/08. Summary of product characteristics. Chlorpromazine, Haloperidol, Trifluoperazine, Sulpiride, Zucolpentixole, Amisulpiride, Aripiprazole, Olanzapine, Risperidone, Quetiapine, Clozapine, Sertindole, Paliperidone, Lithium carbonate, Lithium citrate, Sodium valproate, Carbamazepine. Available from: www.medicines.org.uk. Accessed 6/02/08. Clinical Knowledge Summaries. Psychosis. SCHIN Ltd. Centre for Health Informatics at Newcastle. Available from: http://www.cks.library.nhs.uk. Accessed 6/02/08. Taylor D, Panton C, Kerwin. The Maudsley Prescribing Guidelines, 9th edition. 2007. Informa Healthcare Ltd. National Service Framework. Mental Health. London: Department of Health. 1999. Available from: www.dh.gov.uk. Accessed 6/02/08 Armstrong A, Bishop S, Radhamanohar M. Medication and Risk of Falls in the Older Person. Approved by THPCT & BLT Acute Trust March 2006. Available from: http://10.148.22.36:8080/thpct/prescribing/practice%20tools%20documents/medication%20and%20the%20risk%20of%20falls%20in%20the%20older%20person. pdf Gordhan A, Hossenbaccus Y. Clozapine GP information sheet. Approved by THPCT & BLT Acute Trust April 2006. Available from: http://10.148.22.36:8080/thpct/prescribing/hospital%20only%20drugs/clozapine.pdf Drugs used in psychosis and related disorders index Back to main Index Drugs used in substance dependence for patients with established chemical dependence Tobacco control Opioid substitution and control Alcohol control Withdrawal of benzodiazepines and related drugs Benzodiazepines and related drugs equivalence table Drugs used in substance dependence for patients with established chemical dependence: Tobacco control NRT, varenicline or bupropion should be offered as appropriate, to people who are planning to stop smoking by an appropriately trained Stop Smoking Adviser NRT, varenicline or bupropion should normally be prescribed as part of a programme where the smoker makes a commitment to stop smoking on or before a particular date (target stop date) The prescription of NRT, varenicline or bupropion should be sufficient to last only a few weeks after the target stop date. Normally, this will
be after 2 weeks of NRT therapy, and 3-4 weeks for varenicline and bupropion, to allow for the different methods of administration and mode of action Subsequent prescriptions should be given only to people who have demonstrated, on re-assessment that their quit attempt is continuing Varenicline or bupropion may be offered to people with unstable cardiovascular disorders, subject to clinical judgement Do not favour one medication over another. The Stop Smoking Adviser and client should choose the one that seems most likely to succeed and should take into account: o contraindications and the potential for adverse effects o the client s personal preferences o the availability of appropriate counselling or support o the likelihood that the client will follow the course of treatment o the client s previous experience of smoking cessation aids If a smoker s attempt to quit is unsuccessful using NRT, varenicline or bupropion, do not offer a repeat prescription within 6 months unless special circumstances have hampered the person s initial attempt to stop smoking, when it may be reasonable to try again sooner Do not offer NRT, varenicline or bupropion in any combination Offer advice, encouragement and support, including referral to the NHS Stop Smoking Service, to help people in their attempt to quit
Nicotine Replacement Therapy Bupropion Adjunct to smoking cessation Adjunct to smoking cessation in combination with motivational support Various Tablets Please refer the patient to the following number if help is required for smoking cessation: 0800 169 1943, alternatively their GP surgery or community pharmacist. This is an atypical antidepressant see BNF for contraindications. The risk of seizures is about 0.1% - this must be considered before initiating treatment (includes concomitant use of drugs that lower seizure threshold). There is insufficient evidence to recommend combined use of bupropion & NRT. The MHRA, EMA & FDA have issued a warning to healthcare professionals and patients (Dec 2007) that it has received reports of suicidal ideation, aggressive, and erratic behaviour associated with the use of varenicline for smoking cessation. Varenicline [Champix ] Adjunct to smoking cessation in combination with motivational support Tablets The July 2008 issue of the Drug Safety Update from the MHRA provides a reminder of the reports of suicidal thoughts and behaviour, not only in those with pre-existing psychiatric conditions or other psychosocial risk factors, but also in users of varenicline who have no known pre-existing psychiatric conditions, and in those who continue to smoke. The following advice for healthcare professionals is reiterated: Patients should be told to stop treatment and contact their doctor immediately if they develop suicidal thoughts or behaviour. Varenicline should be stopped immediately if agitation, depressed mood, or changes in behaviour are observed that are of concern to the patient, family, or caregivers. The safety and efficacy of varenicline in people with serious psychiatric illness have not been established; those with such a history should be monitored closely while taking varenicline. MHRA link Click here for a prescribing support information sheet Please see Tower Hamlets PCT Local Enhanced services folder 08/09 as part of the Stop Smoking Local Enhanced Service LES 21 Click here for the latest NICE Smoking cessation services: Quick reference guide
Drugs used in substance dependence for patients with established chemical dependence: Opioid substitution and control Methadone Adjunct in treatment of opioid dependence Sugar free oral solution 1mg/ml Prescribing GP is required to be part of the Substance Misuse Local Enhanced Service. Injectable methadone to be prescribed by the Specialist Addiction Unit only. Buprenorphine Naltrexone Adjunct in treatment of opioid dependence Adjunct to prevent relapse in detoxified formerly opioiddependent patients who have been opioid-free for at least 7-10 days Sublingual tablets [Subutex ] Tablets Prescribing GP is required to be part of the Substance Misuse Local Enhanced Service. Patients must be warned of the risk of acute opioid toxicity occurring in an attempt to overcome the blockade effect of naltrexone. The risk of fatal overdose may be more significant if there are changes in the individual s opioid tolerance level, particularly following a detoxification program and any period of abstinence. Naltrexone to be initiated by the Specialist Addiction Unit only. NICE guidance is available for the management of opioid dependence (2007). Please see Tower Hamlets PCT Local Enhanced services folder 08/09 as part of the Management of Drug and Alcohol Misuse in Primary Care Local Enhanced Service LES 1. Drugs used in substance dependence index Drugs used in substance dependence for patients with established chemical dependence: Alcohol control Vitamin B Co- Oral vitamin therapy post Tablets One tablet three times a day, for a minimum of 7 days. strong parental therapy Oral vitamin therapy post Thiamine Tablets Thiamine 100mg three times a day for a minimum of 7 days. parental therapy
Chlordiazepoxide Diazepam Oxazepam Acamprosate Adjunct in acute alcohol withdrawal Adjunct in acute alcohol withdrawal Adjunct in acute alcohol withdrawal in patients with severe hepatic impairment Maintenance of abstinence in alcohol dependence Tablets, capsules Tablets, oral solution Tablets Tablets Ensure that there is a reducing regime protocol from the community alcohol services in place before prescribing. Chlordiazepoxide may not be appropriate in patients with severe hepatic impairment. Ensure that there is a reducing regime protocol from the community alcohol services in place before prescribing. Diazepam may not be appropriate in patients with severe hepatic impairment. Ensure that there is a reducing regime protocol from the community alcohol services in place before prescribing. Continued alcohol use cancels out any benefit. Treatment is licensed for up to 1 year. Drugs used in substance dependence for patients with established chemical dependence: Withdrawal of benzodiazepines and related drugs Dependence and withdrawal Withdrawal of a benzodiazepine should be gradual because abrupt withdrawal may produce confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal of a barbiturate is even more likely to have serious effects. The benzodiazepine withdrawal syndrome may develop at any time up to 3 weeks after stopping a long-acting benzodiazepine, but may occur within a day in the case of a short-acting one. It is characterised by insomnia, anxiety, loss of appetite and of body-weight, tremor, perspiration, tinnitus, and perceptual disturbances. Some symptoms may be similar to the original complaint and encourage further prescribing; some symptoms may continue for weeks or months after stopping benzodiazepines. A benzodiazepine can be withdrawn in steps of about one-eighth (range one-tenth to one-quarter) of the daily dose every fortnight. A suggested withdrawal protocol for patients who have difficulty is as follows: Transfer patient to equivalent daily dose of diazepam preferably taken at night Reduce diazepam dose every 2 3 weeks in steps of 2 or 2.5 mg; if withdrawal symptoms occur, maintain this dose until symptoms improve Reduce dose further, if necessary in smaller steps; it is better to reduce too slowly rather than too quickly Stop completely; time needed for withdrawal can vary from about 4 weeks to a year or more Counselling may help; beta-blockers should only be tried if other measures fail; antidepressants should be used only where depression or panic disorder co-exist or emerge; avoid antipsychotics (which may aggravate withdrawal symptoms).
Diazepam All other benzodiazepines and related drugs Adjunctive treatments with antidepressants or mood stabilisers Gradual withdrawal of benzodiazepines in polysubstance or long term user Gradual withdrawal of benzodiazepines in polysubstance or long term user with hepatic dysfunction Gradual withdrawal of benzodiazepines in polysubstance or long term user Tablets, oral solution Various Various Patient should be transferred to the equivalent daily dose of diazepam and reduce the dose by 2mg every 3 weeks. Extra precautions apply in patients with hepatic dysfunction as diazepam may accumulate to toxic levels. Diazepam substitution may not be appropriate in this group of patients. Reduce the dose of current benzodiazepine or related drug over at least 4 12 weeks. Contact a mental health specialist for advice Equivalent daily dose of benzodiazepines and related drugs to diazepam 5 mg/day Drug Equivalent dose of 5mg diazepam Alprazolam 0.25mg Chlordiazepoxide 15mg Clobazam 10mg Clonazepam 0.25mg Flurazepam 15mg Loprazolam 0.5 1mg Lorazepam 500 micrograms (0.5mg) Lormetazepam 0.5 1mg Nitrazepam 5mg Oxazepam 15mg Temazepam 10mg Zopiclone 7.5mg Zolpidem 10mg Zaleplon 10mg Based on table from the CKS http://www.cks.library.nhs.uk/benzos_z_drug_withdrawal/view_whole_guidance (accessed 24.01.2008)