4: Central nervous system

Please select a topic:

4.1 Hypnotics and anxiolytics / 4.2 Drugs used in psychoses and related disorders
4.3 Antidepressant drugs / 4.4 Central nervous system stimulants
4.5 Drugs used in obesity
4.6 Drugs used in nausea and vertigo / 4.7 Analgesics
4.8 Antiepileptics / 4.9 Drugs used in parkinsonism and related disorders
4.10 Drugs used in substance dependence / 4.11 Drugs for dementia

Changes to the Formulary since previous version

(5.3.2014)

Section / Change / Reason for change
4.5 / ADDED: Orlistat: theoretical interaction with antiretroviral HIV medicines / MHRA Drug Safety Update

4. Antidepressants - swapping and stopping

General Guidelines

·  All antidepressants have the potential to cause withdrawal phenomena. When taken continuously for six weeks or longer, antidepressants should not be stopped abruptly unless a serious adverse event has occurred (e.g. cardiac arrhythmia with a tricyclic).

·  When swapping from one antidepressant to another, abrupt withdrawal should usually 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.

·  The speed of cross-tapering is best judged by monitoring patient tolerability. No clear guidelines are available, so caution is required.

·  Note that the co-administration of some antidepressants is absolutely contra-indicated, and even cross-tapering of small doses can be dangerous. In other cases, theoretical risks or lack of experience preclude recommending cross-tapering.

·  In some cases cross-tapering may not be considered necessary. An example is when switching from one SSRI to another: their effects are so similar that administration of the second drug is likely to ameliorate withdrawal effects of the first. However, there is little firm evidence of this occurring.

·  Potential dangers of simultaneously administering two antidepressants include pharmacodynamic interactions (serotonin syndrome, hypotension, drowsiness) and pharmacokinetic interactions (e.g. elevation of tricyclic plasma levels by some SSRIs). The serotonin syndrome may include restlessness, diaphoresis, tremor, shivering, myoclonus, confusion, convulsions and death.

The advice given in the following table should be treated with caution and patients should be very carefully monitored when switching.

ANTIDEPRESSANTS – SWAPPING AND STOPPING

To
From / MAOIs-
hydrazines / Tranyl-cypromine / Tricyclics / Citalopram /
Escitalopram / Fluoxetine / Paroxetine
MAOIs-
hydrazines / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks
Tranyl-
cypromine / Withdraw and wait for two weeks / - / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks
Tricyclics / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Cross taper cautiously / Halve dose and add citalopram then slow withdrawal.*2 / Halve dose and add fluoxetine then slow withdrawal.*2 / Halve dose and add paroxetine then slow withdrawal.*2
Citalopram/
Escitalopram / Withdraw and wait for one week / Withdraw and wait for one week / Cross taper cautiously *2 / - / Withdraw then start fluoxetine 10mg/day / Withdraw and start paroxetine at 10mg/day
Paroxetine / Withdraw and wait for two weeks / Withdraw and wait for one week / Cross taper cautiously with very low dose of tricyclic *2 / Withdraw and start citalopram at 10mg/day / Withdraw then start fluoxetine at 10mg/day / -
Fluoxetine*3 / Withdraw and wait five to six weeks / Withdraw and wait five to six weeks / Stop fluoxetine. Wait 4-7days. Start tricyclic at very low dose and increase very slowly / Stop fluoxetine. Wait 4-7 days. Start citalopram at 10mg/day and increase slowly / - / Stop fluoxetine. Wait 4-7 days, then start paroxetine 10mg/day
Sertraline / Withdraw and wait for one week1 / Withdraw and wait for one week / Cross taper cautiously with very low dose of tricyclic *2 / Withdraw then start citalopram at 10mg/day / Withdraw then start fluoxetine at 10mg/day / Withdraw then start paroxetine at 10mg/day

Red = Hospital use only

Green = GP & Hospital use. Drugs not classified as Red, Amber or Green + are classified as Green by default

Amber = Drugs with shared care agreement

Green + = Initiated by Hospital specialist only

Gateshead Health NHS Foundation Trust Page 17 of 43 Date: 17.3.2014

Drug Formulary

To
From / Sertraline / Trazodone / Moclobemide / Reboxetine / Venlafaxine / Mirtazapine / Duloxetine
MAOIs-
hydrazines / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks*1 / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks
Tranyl-
cypromine / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks *1 / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw and wait for two weeks
Tricyclics / Halve dose and add sertraline then slow withdrawal.*2 / Halve dose and add trazodone then slow withdrawal. / Withdraw and wait for one week / Cross taper cautiously / Cross taper cautiously, starting with venlafaxine 37.5mg/day / Cross taper cautiously / Cross taper cautiously, starting with duloxetine 30mg per day. Increasing slowly
Citalopram/
Escitalopram / Withdraw and start sertraline at 25mg/day / Withdraw before starting titration of trazodone / Withdraw and wait at least one week / Cross taper cautiously / Withdraw. Start venlafaxine 37.5mg/day. Increase very slowly / Cross taper cautiously / Abrupt switch possible.Start duloxetine at 60mg per day.
Paroxetine / Withdraw and start sertraline at 25mg/day / Withdraw before starting titration of trazodone / Withdraw and wait at least two weeks / Cross taper cautiously / Withdraw paroxetine. Start venlafaxine 37.5mg/day and increase very slowly / Cross taper cautiously / Abrupt switch possible.Start duloxetine at 60mg per day.
Fluoxetine*3 / Stop fluoxetine. Wait 4-7 days, then start sertraline 25mg/day / Stop fluoxetine. Wait 4-7 days, then start low dose trazodone / Withdraw and wait at least five weeks / Cross taper cautiously / Withdraw. Wait 4-7 days. Start venlafaxine at 37.5mg/day. Increase very slowly / Cross taper cautiously / Abrupt switch possible.Start duloxetine at 60mg per day.
Sertraline / - / Withdraw before starting trazodone / Withdraw and wait at least one week / Cross taper cautiously / Withdraw. Start venlafaxine at 37.5mg/day.
Increase V slowly / Cross taper cautiously / Abrupt switch possible.Start duloxetine at 60mg per day.

*1. Abrupt switching is possible but not recommended.

*2. Do not co-administer clomipramine and SSRIs or venlafaxine. Withdraw clomipramine before starting.

*3. Beware interactions with fluoxetine may still occur for five weeks after stopping fluoxetine because of long half-life.

*5. Withdrawal effects seem to be more pronounced. Slow withdrawal over 1-3 months may be necessary.

Adapted from: Taylor D, Paton C, and Kapur S. The Maudsley Prescribing Guidelines, 11th ed. London: Informa Healthcare, 2012

To
From / MAOIs-
hydrazines / Tranyl-cypromine / Tricyclics / Citalopram /Escitalopram / Fluoxetine / Paroxetine
Trazodone / Withdraw and wait at least one week / Withdraw and wait at least one week / Cross taper cautiously with very low dose of tricyclic / Withdraw then start citalopram at 10mg/day / Withdraw then start fluoxetine at 10mg/day / Withdraw then start paroxetine at 10mg/day
Moclobemide / Withdraw and wait 24 hours / Withdraw and wait 24 hours / Withdraw and wait 24 hours / Withdraw and wait 24 hours / Withdraw and wait 24 hours / Withdraw and wait 24 hours
Reboxetine / Withdraw and wait at least one week / Withdraw and wait at least one week / Cross taper cautiously / Cross taper cautiously / Cross taper cautiously / Cross taper cautiously
Venlafaxine / Withdraw and wait at least one week / Withdraw and wait at least one week / Cross taper cautiously with very low dose of tricyclic *2 / Cross taper cautiously. Start with 10mg/day / Cross taper cautiously. Start with 10mg/day / Cross taper cautiously. Start with 10mg/day
Mirtazapine / Withdraw and wait for two weeks / Withdraw and wait for two weeks / Withdraw then start tricyclic / Withdraw then start citalopram / Withdraw then start fluoxetine / Withdraw then start paroxetine
Duloxetine / Withdraw and wait for at least 5 days / Withdraw and wait for at least 5 days / Cross taper cautiously with very low dose of tricyclic *2 / Withdraw then start citalopram at 10mg per day / Withdraw then start fluoxetine / Withdraw then start paroxetine
Stopping*4 / Reduce over four weeks / Reduce over four weeks / Reduce over four weeks / Reduce over four weeks / At 20mg/day just stop. At higher doses reduce over two weeks / Reduce over four weeks or longer, if necessary*5
To
From / Sertraline / Trazodone / Moclobemide / Reboxetine / Venlafaxine / Mirtazapine / Duloxetine
Trazodone / Withdraw then start sertraline at 25mg/day / - / Withdraw and wait at least one week / Cross taper cautiously / Withdraw . Start venlafaxine at 37.5mg/day / Cross taper cautiously / Cross taper cautiously .Start duloxetine at 30mg per day.
Moclobemide / Withdraw and wait 24 hours / Withdraw and wait 24 hours / - / Withdraw and wait 24 hours / Withdraw and wait 24 hours / Withdraw and wait 24 hours / Withdraw and wait 24 hours
Reboxetine / Cross taper cautiously / Cross taper cautiously / Withdraw and wait at least one week / - / Cross taper cautiously / Cross taper cautiously / Cross taper cautiously
Venlafaxine / Cross taper cautiously. Start with 25mg/day / Cross taper cautiously / Withdraw and wait at least one week / Cross taper cautiously / - / Withdraw before starting mirtazapine cautiously / Withdraw. Start duloxetine 30mg/day. Increase very slowly.
Mirtazapine / Withdraw then start sertraline / Withdraw then start trazodone / Withdraw and wait one week / Cross taper cautiously / Cross taper cautiously / - / Withdraw. Start duloxetine 30mg/day. Increase very slowly.
Duloxetine / Withdraw then start sertraline at 25mg/day / Withdraw then start trazodone / Withdraw and wait one week / Cross taper cautiously / Withdraw, then start venlafaxine / Cross taper cautiously / -
Stopping*4 / Reduce over four weeks / Reduce over four weeks / Reduce over four weeks / Reduce over four weeks / Reduce over four weeks or longer, if necessary*5 / Reduce over four weeks / Reduce over four weeks

4.1 Hypnotics and anxiolytics

Hypnotics

·  Chloral Hydrate 500mg/5ml solution (unlicensed)

·  Clomethiazole/Chlormethiazole 192mg capsule

·  Chloral betaine (Cloral betaine) 707mg tablets

·  Nitrazepam 2.5mg/5ml suspension

·  Nitrazepam 5mg tablets

·  Temazepam 10mg, 20mg tablets

·  Temazepam 10mg/5ml oral solution

·  Zopiclone 3.75mg and 7.5mg tablets (Critical care and Mental Health Only)

·  Melatonin 2mg MR tablets

Dose

-  Chloral hydrate oral solution 500mg/5ml: see BNF.

-  Clomethiazole capsule 192mg; usually 1-2 capsules at bedtime

-  Cloral betaine tablets 707mg: usually 1-2 tablets at bedtime.

-  Nitrazepam tablets 5mg; oral solution 2.5mg/5mL: usually 5-10mg at bedtime

-  Temazepam tablets 10mg, 20mg; oral solution 10mg/5mL: usually 10-20mg at bedtime.

-  Melatonin MR tablets 2mg: 2mg once a day at bedtime

Prescribing notes

·  Non-drug treatments are recommended as 1st line therapy

·  Routine prescribing for insomnia is undesirable and should be used in short courses only when insomnia is severe, disabling, or subjecting the individual to extreme distress.

·  New patients should not be put on a repeat prescription system and existing patients receiving an hypnotic should be reviewed and offered the chance to stop or reduce (see BNF withdrawal protocol).

·  There is no evidence that never hypnotics (zaleplon, zolpidem, zopiclone) provide any additional clinical benefit or a free from dependence.

Anxiolytics

·  Buspirone 5mg tablets (Mental health only)

·  Chlordiazepoxide 5mg and 10mg capsules

·  Diazepam 2mg, 5mg tablets

·  Diazepam 2mg/5ml syrup

·  Diazepam 5mg/ml injection

·  Lorazepam 1mg, 2.5mg tablets

·  Lorazepam 4mg/ml injection

Dose

-  Buspirone tablets 5mg: 5mg 2-3 times daily increased if necessary to max 45mg daily in divided doses.

-  Chlordiazepoxide tablets 5mg, 10mg; capsules 10mg: For Anxiety: 10mg 3 times daily increased if necessary to 60-100mg daily in divided doses.

-  Diazepam tablets 2mg, 5mg; oral solution 2mg/5mL: 2mg 3 times daily increased if necessary to 15-30mg daily in divided doses.

-  Lorazepam tablets 1mg, 2.5mg; injection 4mg/ml: By mouth: 1-4mg daily in divided doses. Injection: see BNF.

Prescribing notes

·  Benzodiazepines are indicated for the short-term relief (2-4 weeks only) of anxiety that is severe, disabling or subjecting the individual to unacceptable distress. The use of benzodiazepines benzodiazepines to treat short-term "mild" anxiety is inappropriate and unsuitable.

·  Treatment should be limited to the lowest dose possible for the shortest possible time.

·  Diazepam has a long duration of action and rapid onset. It is the recommended daytime anxiolytic and is used as premedication before surgery and other procedures.

Older Patients - Hypnotics and anxiolytics
·  Hypnotics and anxiolytics should be avoided in older patients if possible. Older patients can become ataxic, confused and are at increased risk of falling and injuring themselves.
MHRA Drug Safety Update
Addiction to benzodiazepines and codeine: supporting safer use
Article date: July 2011
Summary
Reminder for healthcare professionals:
·  Given the risks associated with the use of benzodiazepines, patients should be prescribed the lowest effective dose for the shortest time possible. Maximum duration of treatment should be 4 weeks, including the dose-tapering phase
·  Over-the-counter codeine-containing medicines should be used for the short-term (3 days) treatment of acute, moderate pain which is not relieved by paracetamol, ibuprofen, or aspirin alone (see Drug Safety Update September 2009)
Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON123123

4.2 Drugs used in psychoses and related disorders

Antipsychotic drugs