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Clinical Guideline / Formulary Document
Pharmacy Department Medicines Management Services
ANXIETY DISORDERS
This guideline covers a range of anxiety disorders, including generalised anxiety disorder, social
anxiety disorder, post-traumatic stress disorder, panic disorder, obsessive–compulsive disorder and
body dysmorphic disorder. Anxiety disorders often co-exist with other psychological symptoms,
especially depressive symptoms. Psychological and pharmacological therapies are used to treat
anxiety disorders.
NICE guidelines suggest a stepped care* approach for managing of anxiety disorders
(*Adapted from NICE CG113 – Anxiety)
Step 1: Identification and assessment; education about anxiety disorder and treatment
options; active monitoring.
Step 2: Use of low-intensity psychological interventions: individual non-facilitated self-help,
individual guided self-help and psychoeducational groups
Step 3: For inadequate response to step 2 interventions or marked functional impairment.
Choice of a high-intensity psychological intervention (CBT/applied relaxation) or a drug
treatment.
Step 4: Complex treatment-refractory anxiety disorder and very marked functional
impairment or a high risk of self-harm; requiring highly specialist treatment
Pharmacological Treatments
Pharmacological treatment of anxiety disorders should be considered for severe and persistent
symptoms which result in occupational and social disability
Psychological interventions should be offered to service users who prefer non-pharmacological
treatment or have not benefited from or are unable to engage with pharmacological
interventions.
The choice of initial treatment should be guided by preference, risks and benefits, side effects,
prior treatment history, presence of other physical and psychiatric conditions, suicide risk,
potential drug interactions and cost.
Discuss the condition and treatment options fully and provide written information.
Selective Serotonin Reuptake Inhibitors (SSRIs) are effective for a range of anxiety disorders
and are suitable first-line treatments.
Inform service users prescribed antidepressants about a delayed onset of effect (at least 2
weeks), likely length of treatment and the need to take medication as prescribed.
Pregabalin is licensed for use in Generalised Anxiety Disorder (GAD). Buspirone is licensed for
the short-term management of anxiety.
People with an anxiety disorder should not be prescribed benzodiazepines or antipsychotics
unless specifically indicated.
Decisions about off-label use of medications for anxiety disorders should be led by guidelines,
evidence from scientific literature and clinical experience. Informed consent to off-label use
should be obtained and documented.
Response to treatment should be assessed and recorded at each review and treatment adjusted
if needed.
Safety Warnings
Antidepressants are associated with an initial worsening of anxiety/agitation and an increased
risk of suicidal thinking and behaviour. Monitor closely particularly at the start of treatment and
when the dose is changed.
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
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Discontinue antidepressants gradually. Abrupt discontinuation (sometimes reduced or missed
doses) of antidepressants can lead to withdrawal symptoms e.g. dizziness, paraethesias,
nausea, headaches, sweating, anxiety and sleep disturbances.
Use antidepressants with care in glaucoma, bipolar disorders, prostate hypertrophy, bleeding
disorders and seizures.
Hyponatraemia has been associated with all antidepressants and should be considered in all
those who develop drowsiness, confusion, or convulsions while on antidepressants.
SSRIs can increase risk of bleeding. Caution is required in older adults and when used in
combination with NSAIDS, aspirin or anticoagulants.
SSRIs can increase risk of falls and osteoporotic fractures in people over 50 years.
Serotonin syndrome (agitation, confusion, tremor, hypereflexia, myoclonus and hyperthermia)
can occur with serotonergic drugs and requires emergency management.
Benzodiazepines are associated with physical and psychological dependence when taken
regularly for more than a few weeks. Avoid prolonged use. Withdrawal of a benzodiazepine
should be gradual because abrupt withdrawal may produce confusion, toxic psychosis,
convulsions, or a condition resembling delirium tremens.
A paradoxical increase in hostility and aggression may be reported by patients taking
benzodiazepines. The effects range from talkativeness and excitement to aggressive and
antisocial acts. Adjustment of the dose (up or down) sometimes attenuates the impulses.
Increased anxiety and perceptual disorders are other paradoxical effects.
Cases of misuse, abuse and dependence have been reported with pregabalin.
Psychotropic drugs may impair the mental or physical abilities required for the performance of
potentially hazardous tasks such as driving a car or operating machinery, the patient should be
cautioned accordingly.
Adverse Effects and Interactions
SSRIs are better tolerated and safer in overdose than other antidepressants.
Common side effects of SSRIs are headache, nausea, and anxiety/agitation, especially when
starting treatment (usually settle on continued treatment). Other side effects are insomnia,
tremor, akathisia, sweating, paraethesias, sexual dysfunction, including diminished libido and
difficulty with erection and orgasm, muscle/joint pain, weight gain and manic or psychotic
symptoms.
Tricyclic antidepressants have similar efficacy to SSRIs but are more likely to be discontinued
because of side-effects and are toxic in overdose. Common side effects of tricyclics include
anxiety, drowsiness, dizziness, agitation, confusion, anticholinergic effects (dry mouth,
constipation, urinary retention and blurred vision); cardiovascular effects (hypotension,
tachycardia, arrhythmias and other ECG changes - baseline ECG is advised, where
appropriate); hepatic effects, changes in blood sugar, increased appetite, weight gain and
sexual dysfunction.
Monoamine Oxidase Inhibitors (MAOIs) can have dangerous interactions with some foods and
drugs, and should be reserved for initiation by consultants. Service users prescribed MAOIs
require careful monitoring (blood pressure) and advice on dietary and drug interactions. When
changing antidepressants, a suitable washout period (usually at least 14 days) should be
allowed before or after using MAOIs.
All people prescribed antidepressants, should be informed, at the time that treatment is initiated,
of potential side effects and discontinuation/withdrawal symptoms (particularly with paroxetine).
Monitor for akathisia, anxiety, agitation, increased suicide risk and other side effects.
People prescribed antidepressants should be reviewed after 2 weeks and regularly thereafter eg
every 2–4 weeks in the first 3 months and at greater intervals if response is good. People
considered to be at increased suicide risk should be seen after 1 week and frequently thereafter
until the risk is no longer considered significant.
Due to risk of dependence, tolerance, withdrawal and rebound symptoms, benzodiazepines
should be reserved for short-term use (two to four weeks only) at the lowest effective dose for
anxiety that is severe, disabling, or causing unacceptable distress. Benzodiazepines can cause
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
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sedation, fatigue, ataxia, slurred speech, and risk of falls and fractures. Long term use can
cause memory impairments, dependence, impaired alertness and impaired ability to perform
skilled tasks (e.g. driving)
Mirtazapine has few antimuscarinic effects, but causes sedation during initial treatment and is
associated with weight gain and blood dyscrasias.
Antipsychotics may be used with caution in anxiety with agitation or psychotic symptoms.
Pregabalin treatment has been associated with dizziness and somnolence. There have also
been post-marketing reports of loss of consciousness, confusion and mental impairment.
Increased appetite, increased weight, suicidal thoughts and behavior have been reported. Other
adverse effects reported include: vision-related effects and gastrointestinal effects.
Specific Phobias
Simple or specific phobias are usually unresponsive to pharmacological treatments and respond
better to behavioural therapy, although paroxetine or benzodiazepines may be considered for
disabling phobias unresponsive to psychological approaches
General Anxiety Disorder (GAD)
A stepped-care approach is recommended by NICE for the management of GAD, offering the
least intrusive, most effective intervention first with non-drug interventions the mainstay of
treatment for many people with GAD.
A high-intensity psychological intervention (e.g. CBT) or drug treatment is recommended for
people with GAD and marked functional impairment, or those whose symptoms have not
responded adequately to low intensity psychological interventions.
Discuss the treatment options, side effects, potential interactions and any concerns with the
service user and provide the relevant medication information leaflet.
SSRIs are the first-line treatments for GAD. NICE recommends sertraline as the drug of choice
(off-label) as it has proved clinically effective in the use of mixed anxiety and depressive disorder
and it is the most cost-effective drug.
If sertraline is ineffective, offer an alternative SSRI (e.g. escitalopram or paroxetine) or an SNRI
(venlafaxine or duloxetine), taking into account the following factors:
o side-effect profile and potential for drug interactions
o the person's prior experience of treatment with individual drugs (particularly adherence,
effectiveness, side effects, experience of withdrawal symptoms and personal preference).
o risk of a withdrawal syndrome (especially with paroxetine and venlafaxine)
o the risk of suicide and likelihood of toxicity in overdose (especially with venlafaxine)
If the person cannot tolerate SSRIs or SNRIs, consider offering pregabalin.
Use low initial doses of antidepressant and titrate up slowly. Initial worsening of anxiety may be
evident.
Antidepressants can take several weeks to have an effect. The full anxiolytic effect will develop
gradual over 1 week or more. If a drug is effective, it should be continued for at least a year as
the likelihood of relapse is high.
If there is severe anxiety that is disabling and causing the person significant distress, consider
prescribing short-term treatment with a benzodiazepine (for example diazepam). Prescriptions of
short duration should be given, with regular review of the patient, and treatment should last no
longer than 2 to 4 weeks.
For people starting on an antidepressant, initially review after two weeks (one week if aged
under 30 years or risk of suicide)
Review the effectiveness and side effects of medication every 2–4 weeks during the first 3
months of treatment and every 3 months thereafter.
Optimising the dose of medication, switching to an alternative drug, or stopping drug treatment
is recommended if there is no improvement of anxiety symptoms after 2 months of treatment.
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
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If treatment is effective and tolerable, continue for at least 1 year as risk of relapse is high.
If there is a partial response to drug treatment, consider offering a high-intensity psychological
intervention in addition to drug treatment.
Alcohol or substance misuse should be managed first as it may be contributing to the symptoms
of GAD.
Treat the primary disorder first (that is, the one that is more severe and in which it is more likely
that treatment will improve overall functioning).
Relevant NICE Guidance
NICE Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults.
CG113 (2011). Available from www.nice.org.uk/guidance/CG113.
NICE pathways: Generalised anxiety disorder
http://pathways.nice.org.uk/pathways/generalised-anxiety-disorder.
NICE quality standards [QS53]. Anxiety disorders. February 2014. Available from:
http://www.nice.org.uk/guidance/qs53.
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
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Generalised Anxiety Disorder
First Line:
Relative Cost
Notes
Sertraline
£
Not currently licensed for the treatment of GAD (off-label use); Recommended first-line by NICE
If successfully treated previously with another antidepressants, re-initiate prior therapy
Offer high-intensity psychological intervention and anxiety management techniques
Second Line:
Relative Cost
Notes
Alternative SSRI
Paroxetine
liquid
Escitalopram
liquid
Citalopram
liquid
Fluoxetine
liquid
or SNRI
Venlafaxine
Tablets
XL caps/MR tabs
Third Line:
£
£££
£
£££
£
££
£
£
Duloxetine
Brand
Pregabalin
££
£££
££££
Trazodone
liquid
Imipramine
Offer another SSRI not tried first-line if unable to tolerate treatment or no response after 12 weeks at
optimal dose. Checking adherence; confirm diagnosis; if partial response consider dose increase
Use lower initial doses; high likelihood of discontinuation reactions
Consider preference, side effects - including QT effects and previous response
Off-label use; obtain consent; consider side effects - including QT effects and previous response
Off-label use; obtain consent; consider long half life, preference, side effects and previous response
Monitor blood pressure
More toxic in overdose than SSRIs; High risk of discontinuation reactions
£
££
Relative Cost
££
££££
£
Notes
Monitor blood pressure
NICE recommends pregabalin only if SSRIs or SNRIs not tolerated; somnolence and dizziness are
common. Risk of dependence and misuse. Costs are significantly greater than those for generic
SSRI; Twice daily with single capsule dosing is required when discharging patients to GP.
Consider after non-response to or poor tolerance of SSRI treatment ; sedating
Off-label use. Avoid tricyclics if risk of suicide; potential for cardiac and CNS toxicity in overdose
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
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Generalised Anxiety Disorder
Other Agents
Benzodiazepines
eg Diazepam/Lorazepam
Liquids
Quetiapine
Tabs
M/R
Branded
Buspirone
Propranolol
M/R
Liquid
Hydroxyzine
Relative Cost
£
£££
£
££-£££
£££
£
£
££
£££
£
Notes
Not routinely recommended except as a short-term measure during crisis because of risk of side
effects, dependence and misuse. Useful adjuncts in agitated service users.
Off-label use - limited evidence of benefits; greater risk of discontinuation due to side effects. Only for
use in specialist settings.
For short-term use only – delayed onset of action; greater risk of discontinuation due to side effects;
Efficacy is reduced in previous extensive use of benzodiazepines; may be useful where
benzodiazepines not used before
May be useful for somatic symptoms particularly tachycardia; check contraindications
Limited effectiveness; use for sedative effect inappropriate. MHRA/CHM advice: Risk of QT-interval
prolongation and torsade de pointes
Treatment Refractory Generalised Anxiety Disorder
Relative Cost
Notes
Review current and past treatments and adherence. Increase the dose of the current treatment to the
maximum dose; Switch to an alternative evidence-based treatment not previously tried
Use a combination of psychological interventions and drug treatments.
Antidepressant
combinations
Antidepressant +
Antipsychotic
£-£££
Seek consultant advice. Limited evidence and side effects and interactions more likely
£-£££
Consultant initiation only. Do not use routinely due to limited evidence of effect; Side effects and
interactions more likely. Long-term use of antipsychotic should be avoided.
Antidepressants +
other agents, e.g.
buspirone, diazepam,
pregabalin etc
£-£££
Seek consultant advice. No clear evidence of benefit. Check for contraindications
General principles
Mersey Care Clinical Guideline / Formulary Document
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Updated: Jan 2017
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Panic Disorder with or without Agoraphobia
Psychological therapies, drug treatment and self-help are options for treatment of panic
disorder.
Pharmacologic treatments may be considered if behavioural or cognitive therapy fails.
Before prescribing drug treatment, consider age, previous treatment response, risk of overdose,
tolerability, potential interactions with concomitant medications, service user preference and
costs.
Unless otherwise indicated, an SSRI licensed for panic disorder should be first line treatment.
To minimise risk of side effects, treatment should be started at a low dose and the dose
increased slowly until a satisfactory therapeutic response is achieved.
Long-term treatment and doses at the higher end of the recommended range may be necessary
when standard doses are inadequate.
There may be an initial exacerbation of anxiety and panic symptoms
It can take several weeks before the effects of antidepressants are evident
When new medication is started, efficacy and side-effects should be reviewed within 2 weeks of
initiation and again at 4, 6 and 12 weeks.
Treatment should be reviewed at 8–12 weeks intervals if drug used for more than 12 weeks
If there is no improvement after 12 weeks, switch to an alternative antidepressant.
Remission of symptoms may take up to 6 months or longer (including 4–6 weeks at the highest
comfortably tolerated dose).
Medication should be continued for 6 months to 1 year at the optimal dose after acute response
to reduce the risk of recurrence before the dose is gradually reduced. Long-term treatment and
monitoring may be necessary for some people.
Antidepressants for panic disorder should be discontinued over at least 4 weeks
Benzodiazepines, sedating antihistamines or antipsychotics should not be prescribed for the
treatment of panic disorder.
Relevant NICE Guidance
NICE Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults.
NICE clinical guideline 113 (2011). Available from www.nice.org.uk/guidance/CG113
NICE Pathways: Panic disorder
http://pathways.nice.org.uk/pathways/panic-disorder
NICE quality standards [QS53]. Anxiety disorders. February 2014. Available from:
http://www.nice.org.uk/guidance/qs5
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
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Panic Disorder
First Line:
SSRI
e.g.
Sertraline
Citalopram
Escitalopram
Paroxetine
Relative Cost
Liquid formulations
Second Line:
££-£££
Relative Cost
Imipramine
£
Not licenced for panic disorder but has shown long-term benefit. Consider when an SSRI is not
suitable or there is no improvement after a 12-week course and further medication is appropriate;
Clomipramine
£
Reboxetine
Venlafaxine
Tablets
XL capsules/MR tabs
Third Line:
£££
Not licenced for panic disorder but has shown benefit. Consider when an SSRI is not suitable or
there is no improvement after a 12-week course
Some benefit but less effective than SSRIs; Risk of hypotension and hypokalaemia
Monitor blood pressure; cardiotoxic in overdose
Mirtazapine
Tabs/orodispersible
Liquid
MAOIs
Moclobemide
Phenelzine
Propranolol
M/R
Liquid
Benzodiazepines
Tablets
Liquid
£
£
£
£
£
££
Relative Cost
Notes
Offer psychological therapies and encourage self help
Consider preference, previous response, side effects and potential interactions
Start with low doses then gradually increase to a full dose, as tolerated
Citalopram is more cardiotoxic than other SSRIs and can cause QT prolongation at higher doses
Paroxetine has a short half life and a high risk of withdrawal symptoms
Fluoxetine and fluvoxamine are not licenced for panic disorder; may be tried if previous good
response shown. Consider long half life when switching or stopping fluoxetine. GI side effects are
common with fluvoxamine; bradycardia and ECG changes have been noted
Notes
Notes
Not licenced for panic disorder but has shown some benefit; sedating; risk of weight gain
£
£££
££
££
£
££
£££
£
£££
Risk of drug interactions and other dietary restrictions limit use; allow a sufficient washout period.
Only consider when unresponsive or intolerant to several treatment options
Limited evidence but may reduce somatic effects; check contraindications
Benzodiazepines should not be prescribed except for short term use in severe, distressing and
disabling panic symptoms
Mersey Care Clinical Guideline / Formulary Document
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Panic Disorder
Not Recommended:
Relative Cost
Notes
Antihistamines
Antipsychotics
Benzodiazepines
£-£££
Sedating antihistamines or antipsychotics should not be prescribed for the treatment of PD
Benzodiazepines should not be prescribed except as above due to unfavourable outcomes
Treatment Refractory Panic Disorder
Strategy
Relative Cost
Assessment
Notes
Consider and manage comorbidity e.g. depression
Review current and past treatments and adherence
Increase the dose of the current treatment to the maximum dose;
Use a combination of psychological interventions and drug treatments. However, there is little
evidence to support the use of pharmacological and psychological interventions in combination
Dose escalation
£-£££
No clear benefit
Switching
£-£££
Switching to an alternative agent with proven efficacy may be helpful
Augmentation
£-£££
Add a benzodiazepine e.g. diazepam, lorazepam, clonazepam or buspirone or CBT
Antidepressant
combinations
£-£££
Seek consultant advice. Side effects and interactions more likely.
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
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Social Anxiety Disorder (SAD)
Initial treatment involves individual cognitive behavioural therapy (CBT) developed specifically to
treat social anxiety disorder
Pharmacological treatment may be considered if the social anxiety disorder (social phobia)
interferes significantly with social and occupational activities and if behavioural or cognitive
therapy fails or is declined by the service user.
SSRIs (escitalopram or sertraline) are considered to be the drugs of choice for the treatment of
social anxiety disorder.
If there is only a partial responded to an SSRI (escitalopram or sertraline) after 10 to 12 weeks
of treatment, an individual CBT in addition to the SSRI may be considered.
If symptoms have not responded to an SSRI or service user cannot tolerate the side effects, an
alternative SSRI (e.g. paroxetine, fluvoxamine) or a serotonin noradrenaline reuptake inhibitor
(SNRI), e.g. venlafaxine may be offered. And if still no response, a monoamine oxidase inhibitor
(e.g. phenelzine or moclobemide) may be tried. Dietary and drug interaction advice should be
provided.
The tendency of paroxetine and venlafaxine to produce a discontinuation syndrome (which may
be reduced by extended-release preparations and the risk of suicide and likelihood of toxicity in
overdose should be considered.
There may be an initial exacerbation of anxiety and agitation. Arrange regular meetings with
service user to monitor for adverse effects.
Monitor the risk of suicidal thinking and self-harm regularly.
Standard antidepressant starting doses are indicated for social phobia
Advise and support service users to engage in graduated exposure to feared or avoided social
situations.
Treatment should be continued for at least 9 months and possibly longer in some cases.
Co-morbidities e.g. depression, alcohol and substance misuse should be appropriately
managed.
Relevant NICE Guidance
NICE. Social anxiety disorder: recognition, assessment and treatment. NICE clinical guidelines
CG159 May 2013 Available from https://www.nice.org.uk/guidance/cg159
NICE Pathways: Social anxiety disorder. http://pathways.nice.org.uk/pathways/social-anxietydisorder
NICE quality standards [QS53]. Anxiety disorders. February 2014. Available from:
http://www.nice.org.uk/guidance/
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
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Social Anxiety Disorder (Social Phobia)
First Line:
Relative Cost
SSRI e.g.
Escitalopram (liquid)
Sertraline
£ (£££)
£
Second Line:
Relative Cost
Notes
Offer psychological interventions - CBT is known to be efficacious for long-term treatment
SSRIs considered to be the drugs of choice for the treatment of social anxiety disorder
Consider combining SSRI + CBT in those with high risk of relapse
Continue treatment for 10-12 weeks
Notes
Alternative SSRI
Paroxetine (liquid)
Fluvoxamine
£ (£££)
££
Offer another SSRI not tried first-line if not response to first line treatment or not tolerated
High risk of discontinuation reactions
Risk of nausea and vomiting higher with fluvoxamine than other SSRIs; Risk of interactions.
Unlicensed for the treatment of social anxiety disorder
SNRIs
Venlafaxine (MR)
Third Line:
£ (££)
Relative Cost
Monitor blood pressure. High risk of discontinuation reactions; cardiotoxic in overdose
Notes
MAOIs e.g.
Phenelzine
Moclobemide
££
££
Fluoxetine
liquid
£
££
Other agents
Relative Cost
Consider MAOIs when there is no response or intolerance to previous treatments. Delayed effects
Phenelzine has proven efficacy but side effects, interactions and dietary restrictions limit use.
Phenelzine is unlicensed for the treatment of social anxiety disorder
Moclobemide is licensed for social anxiety disorder and has reduced need for dietary restrictions
Evidence-based proven efficacy. NICE acknowledges its efficacy but does not mention it as
recommended treatment. Fluoxetine is recommended by BAP as a possible choice among other
SSRIs. Fluoxetine is unlicensed for the treatment of social anxiety disorder.
Notes
Anticonvulsants
Buspirone
Clonazepam
Propranolol
Liquid
£-£££
££
£-££
£-££
£££
Consultants only may consider gabapentin; pregabalin
Consider adding buspirone after partial response to SSRI
Short term use only for severe anxiety as an augmentation strategy; risk of dependence
May be useful for somatic symptoms such as tachycardia, sweating and tremor in performancerelated anxiety; check contraindications
Mersey Care Clinical Guideline / Formulary Document
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Treatment-Refractory Social Anxiety Disorder (Social Phobia)
Strategy
Relative Cost
Notes
Dose escalation
£-££
Optimise dose although evidence of benefit is unclear
Switching
£-£££
Adding, or switching to, an alternative pharmacological treatment
Combination
£-£££
Use combinations of antidepressants only where there are no contraindications
Augmentation
£-£££
Consider antidepressant + benzodiazepine or buspirone or a psychological intervention e.g. CBT
Other
£-£££
Consider and manage co-morbidities
Mersey Care Clinical Guideline / Formulary Document
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Obsessive Compulsive Disorder
Psychological interventions (e.g. individual or group CBT) are recommended for mild functional
impairment.
Drug treatment is appropriate for those with poor response to psychological interventions or with
moderate to severe functional impairment.
A combination of pharmacological, behavioural, and psychosocial methods appears to have the
most successful long-term outcome.
Fluoxetine, fluvoxamine, paroxetine, sertraline, and citalopram are recommended by NICE
guidelines for first-line pharmacological treatment of OCD.
Serotonin and noradrenaline re-uptake inhibitors (SNRIs), including venlafaxine should not
normally be used to treat obsessive compulsive disorder without comorbidity.
Clomipramine may be considered when an adequate trial of at least one SSRI was ineffective,
or an SSRI was poorly tolerated, or the patient prefers clomipramine, or there has been a
previous good response. Clomipramine is more toxic than SSRIs and should be avoided if
possible, in people at significant risk of suicide; only prescribe small amounts if clomipramine is
necessary. Blood pressure and an electrocardiogram (ECG) should be checked before
prescribing clomipramine for adults at significant risk of cardiovascular disease. Do not prescribe
in cases of recent myocardial infarction, arrhythmia (particularly heart block), or hypotension.
Doses at the upper end of the indicated dose range and a longer duration of treatment (at least
12 weeks) for an initial response may be necessary.
Monitor for response, adverse effects, worsening anxiety, suicidal thoughts, and self harm
Most people will not experience substantial improvement until 4–6 weeks after starting
medication, and others may show little improvement for up to 12 weeks.
If successful, pharmacological treatment should be continued for 1–2 years (at least 12 months)
to prevent relapse and allow further improvements before considering a gradual taper off over
1–2 months while monitoring for exacerbation or return of symptoms.
Discontinuation of treatment should be carefully considered. Most people with require continued
treatment of some form. Gradual withdrawal over several months may be more successful if
also receiving psychological/behavioural therapies.
Relevant NICE Guidance
NICE Obsessive-compulsive disorder: Core interventions in the treatment of obsessive
compulsive disorder and body dysmorphic disorder. NICE: clinical guideline 31 (2005).
Available from https://www.nice.org.uk/guidance/cg31.
NICE Pathways. Obsessive-compulsive disorder and body dysmorphic disorder.
http://pathways.nice.org.uk/pathways/obsessive-compulsive-disorder
NICE quality standards [QS53]. Anxiety disorders. February 2014. Available from:
http://www.nice.org.uk/guidance/
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
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13
Obsessive Compulsive Disorder (OCD)
First Line:
Relative Cost
Notes
SSRI
Fluoxetine
Sertraline
Paroxetine
Escitalopram
Fluvoxamine
Citalopram (unlicensed)
£
£
£
£
££
£
If CBT is not accessible or available, offer drug treatment. Also offer CBT if medication not preferred
and service users able to engage with CBT
Citalopram and escitalopram cause dose-dependent QT interval prolongation
Fluoxetine has a long half life.
Paroxetine can cause more weight gain and anticholinergic side effects than are other SSRIs and
greater risk of withdrawal symptoms.
Fluvoxamine may cause more side effects (e.g., insomnia, nausea, vomiting) and interactions than
other SSRIs.
Liquid formulations
££-£££
Second Line:
Relative Cost
Notes
Alternative SSRI
Liquids
Clomipramine
£-££
££-£££
£
Offer SSRI not tried first line or escitalopram (NB: costs greater than for generic SSRIs)
Consider clomipramine when SSRI ineffective or poorly tolerated or when it is the preferred option or
where previous good response has been shown. Clomipramine is more likely to induce
anticholinergic effects and can cause hypotension and postural dizziness. It can increase levels of
liver transaminases and has a potential for seizures and cardiac arrhythmias, particularly at higher
doses.
Consider ECG and blood pressure monitoring in cardiovascular disease
Mersey Care Clinical Guideline / Formulary Document
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Obsessive Compulsive Disorder (OCD) continued
Third Line:
Combinations e.g.
SSRI + clomipramine
SSRI + mirtazapine
Augmentation e.g.
SSRI + antipsychotic
SSRI + trazodone
SSRI+ lamotrigine
SSRI + pregabalin
Benzodiazepines e.g.
clonazepam; diazepam
MAOIs
Phenelzine
Venlafaxine
Relative Cost
Notes
£-££
£-£££
Consultant initiation only- monitor carefully – risk of additive side effects and toxicity;
Off-label use- mirtazapine can also be considered
Antipsychotics (risperidone, quetiapine, haloperidol, aripiprazole) can be considered as augmentation
strategy where response to SSRI treatment is poor or incomplete
May be helpful in alleviating OCD and anxiety as well as sleep disturbances
Modest evidence, consider on a individual basis when other strategies have failed
Modest evidence, consider on a individual basis when other strategies have failed
Benzodiazepines are not routinely recommended due to limited evidence for efficacy. Only consider
for short periods for severe anxiety
Consider phenelzine when other strategies have failed and the patient shows atypical obsessive
symptoms eg asymmetry. Should not normally be used without comorbidity
Not routinely recommended. More toxic in overdose than SSRIs. High risk of discontinuation
reactions. NICE states that SNRIs should not normally be used without comorbidity
£-£££
£-£££
£-££
££££
£ (liquids £££)
££
£-££
Treatment-Refractory Obsessive Compulsive Disorder
Strategy
Relative Cost
Notes
Dose escalation
£-£££
Optimise dose – higher than licensed doses may be required - off-label use. Monitor for side effects
and toxicity.
Switching
£-£££
Switch to another pharmacological treatment or psychological treatment nor previously tried
Combination
£-£££
Augmentation
(less evidence)
£-£££
Use drug combinations where not contraindicated or combine with psychological treatment.
Combination of drug treatment with psychological interventions (CBT) may be required. A
combination of SSRIs and CBT is superior to monotherapy and can reduce relapse
Consultant may consider adding an antipsychotic (e.g. risperidone , aripiprazole) to SSRI or
clomipramine - increased risk of side effects; adding lamotrigine, topiramate or buspirone
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
15 |
Post-Traumatic Stress Disorder
Post-traumatic stress disorder (PTSD) develops following a stressful event or situation of an
exceptionally threatening or catastrophic nature. A number of PTSD sufferers may recover with
watchful waiting or limited interventions. However, without effective treatment, many may develop
chronic problems over many years. Drug therapy is largely aimed at managing accompanying
symptoms of anxiety or panic disorder or depression or drug/alcohol misuse.
Pharmacological treatments should be offered to people who:
o express a preference not to engage in trauma-focused psychological treatment
o cannot start psychological therapy because of serious ongoing threat of further trauma
o have gained little benefit from a course of trauma-focused therapy
Drug treatments should also be considered:
o in the acute phase of PTSD for the management of sleep disturbance
o as an adjunct to psychological treatment in adults where there is significant comorbid
depression or severe hyperarousal that impacts on a sufferer’s ability to benefit from
psychological treatment
NICE recommends the use of paroxetine, mirtazapine (unlicensed indication), amitriptyline
(unlicensed indication), or phenelzine (unlicensed indication) in people who refuse
psychotherapy, where psychotherapy is inappropriate or ineffective, or as adjunctive therapy in
significant comorbid depression or severe hyperarousal.
Lower initial dose are recommended although higher target doses (within approved limits) may
prove necessary for full effect.
Treatment periods of 8-12 weeks are needed to assess efficacy
If there is a good response, continue treatment for at least 12 months before gradual withdrawal.
Effectiveness and tolerability should be assessed regularly throughout treatment.
Paroxetine is associated with significant withdrawal (discontinuation) symptoms.
Side effects and the need to follow dietary restrictions limit the use of phenelzine and it should
generally be reserved for patients who have not responded to, or have proved intolerant of other
treatment approaches.
Continued use of an antidepressant should be reviewed if the person with PTSD develops
marked and/or prolonged akathisia.
Where sleep is a major problem for an adult PTSD sufferer, offer advice on sleep hygiene;
hypnotic medication may be appropriate for short-term use only but if required in the long-term,
use of a suitable sedative antidepressant (e.g. mirtazapine) should be considered to reduce risk
of dependence.
Psychological therapies should be used for young people with PTSD. Drug treatments must not
routinely be prescribed.
Relevant NICE Guidance
NICE. Post-traumatic stress disorder: the management of PTSD in adults and children in
primary- NICE clinical guideline 26 (2005). Available from
http://www.nice.org.uk/Guidance/CG26
NICE Pathways. Post-traumatic stress disorder. http://pathways.nice.org.uk/pathways/posttraumatic-stress-disorder.
NICE quality standards [QS53]. Anxiety disorders. February 2014. Available from:
http://www.nice.org.uk/guidance/
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
16 |
Post Traumatic Stress Disorder (PTSD)
First Line:
Relative Cost
Notes
Offer trauma-focused psychological therapies before drug treatment
SSRI e.g.
Paroxetine (liquid)
Sertraline
Mirtazapine
Tabs/Orodispersible
Liquid
Second Line:
Alternative SSRI
Citalopram
Fluoxetine
Venlafaxine (M/R)
£ (£££)
£
Continue drug treatment for 12 months if response is evident at 12 weeks
Paroxetine and sertraline have current licences for PTSD
Off-label use; sedation and weight gain likely; blood dyscrasias - monitor
£
£££
Relative Cost
£
£
£ (££)
Notes
If first line SSRI unsuccessful, an suitable alternative SSRI e.g. citalopram or fluoxetine (off-label
use) can be tried
Venlafaxine may be considered as an alternative to SSRIs following non-response - preferred over
tricyclics or MAOIs as less adverse effects
Monitor for side effects; potentially cardiotoxic
Amitriptyline or
Imipramine
MAOIs i.e.
phenelzine
£
£
£
Consultant only; Can reduce traumatic recollections and nightmares, and repress flashbacks; MAOI
treatment requires careful BP monitoring and advice on drug and food interactions
Other Treatments
Relative Cost
Notes
Hypnotics
liquids
Benzodiazepines
£
££-£££
£ (liquids £££)
May be appropriate for short-term use only where lack of sleep is a major problem; risk of
dependence
May be helpful for short-term management of severe anxiety; risk of dependence and misuse
Propranolol
Liquid
Antiepileptic drugs
£-££
£££
£-£££
Consider for preventing post-traumatic symptoms if there are no contra-indications
Carbamazepine, valproate, topiramate – limited benefits in some benefits; off-label for specific
symptom clusters; e.g. hyper-reactivity, violent behaviour, angry outbursts, avoidance (social
withdrawal) and intrusion
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
17 |
Treatment-Refractory Post Traumatic Stress Disorder
Strategy
Relative Cost
Notes
Dose escalation
£-£££
Consider increasing the dosage within approved limits if tolerated. No clear evidence of benefit.
Switching
£-£££
Consider switching to a different class of antidepressant treatment or using psychological therapy
Combination
£-£££
Seek consultant advice.
Use combinations of medication where there are no contraindications
Consider adding psychological treatment especially where there is comorbid depression or severe
hyperarousal
Augmentation
£-£££
Consider adding a second generation antipsychotic – consultant initiation only.
e.g. add olanzapine to reduce post-traumatic and depressive symptoms and sleep disturbance OR
risperidone in those with coexisting psychotic symptoms or aggression
OR as an adjunct to SSRI antidepressants in refractory cases;
Antipsychotics may also be considered where paranoia or flashbacks are prominent
BAP guidelines also recommend adding prazosin in reducing nightmares and other PSTD symptoms
Co-morbidities
£-£££
Review and manage co-morbidities e.g. sleep disorders, severe depression, anxiety, self harm and
substance misuse.
Consider treating PTSD first unless depression is so severe that it makes psychological treatment
very difficult, in which case treat the depression first.
Treat any significant drug or alcohol problem before treating the PTSD
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
18 |
Appendix 1
Pharmacological Agents For Anxiety Disorders – Licensed Indications And Doses
Drug (SSRIs)
Licensed Indications
Citalopram
 Panic Disorder (PD)
with or without
agoraphobia
 Depressive illness
Escitalopram
 General Anxiety
Disorder (GAD)
 Panic Disorder with or
without agoraphobia.
 Obsessive Compulsive
Disorder OCD
 Social phobia/ Social
Anxiety Disorder (SAD)
 Depressive illness
 Obsessive Compulsive
Disorder (OCD)
 Post Traumatic Stress
Disorder (PTSD)
 Panic Disorder with or
without agoraphobia.
 Social phobia/ Social
Anxiety Disorder (SAD)
 Depressive illness
Sertraline
Dose Recommendations
GAD
PD
Initially 10 mg/day for
first week, gradually
increased in 10mg
steps; recommended
dose 20-30 mg daily;
max 40mg daily and
20mg if over 65yrs
OCD
SAD
Initially 10 mg/day.
max 20 mg/day
Elderly and hepatic
impairment - half
the usual dose and
lower max. dose
Initially 5mg/day
increased to 10mg
after 7 days, max
20mg od.
Elderly and hepatic
impairment - half the
usually dose and
lower max. dose of
10mg
Initially 10 mg/day.
max 20 mg/day
Elderly and hepatic
impairment - half the
usually dose and
lower max. dose
hepatic impairment –
half adult dose
Initially 10mg/day
adjusted after 2-4
weeks; Usual dose
5-20mg.max 20mg
Elderly - efficacy
not studied
hepatic impairment
– half adult dose
Initially 25mg/day
increased after one
week to 50mg/day
May be further
increased in steps of
50mg at intervals of at
least one week, max
200mg/day.
Initially 50mg/day
Dose may be
increased by 50mg
increments at
intervals of at least
one week, max
200mg/day
Initially 25mg/day
increased after one
week to 50mg/day
May be further
increased in steps
of 50mg at
intervals of at least
one week, max
200mg/day.
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
19 |
PTSD
Initially 25mg/day
increased after
one week to
50mg/day
May be further
increased in
steps of 50mg at
intervals of at
least one week,
max 200mg/day
Appendix 1 continued.
Pharmacological agents for anxiety disorders – licensed indications and doses
Drug
(SSRIs)
Licensed
Indications
Dose Recommendations
GAD
PD
OCD
SAD
Fluvoxamine
Obsessive
Compulsive Disorder
(OCD)
Depressive illness
-
-
-
Fluoxetine
Obsessive
Compulsive Disorder
(OCD)
Depressive illness
Bulimia nervosa
-
Initially 10mg daily
increased to 20mg/day
after a week; further
increases to 60 mg daily
(unlicensed use)
Initially 50 in the
evening. May be
gradually increased
to a maximum of
300 mg. Usual dose
100-300mg. Total
daily dose of more
than 150mg is given
in 2-3 divided
doses.
20mg /day, max
usually 40mg od,
but 60mg od has
been used. Up to 80
mg daily has been
used, sometimes
divided into 2
doses.
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
20 |
-
PTSD
Pharmacological agents for anxiety disorders – licensed indications and doses
Drug
(SSRIs/SNRIs)
Paroxetine
Duloxetine
Venlafaxine
Licensed
Indications
General Anxiety
Disorder (GAD)
Panic Disorder
(PD)
Obsessive
Compulsive
Disorder (OCD)
Social Anxiety
Disorder (SAD)
Post Traumatic
Stress Disorder
(PTSD)
Depressive illness
General Anxiety
Disorder (GAD)
Depressive illness
General Anxiety
Disorder (GAD)
Panic Disorder with
or without
agoraphobia.
Social Anxiety
Disorder (SAD)
Depressive illness
Dose Recommendations
GAD
Initially
20mg/day,
(limited efficacy
at higher doses)
further increases
in increments of
10 mg at intervals
of at least one
week to a
maximum of
50mg/day (40mg
od in elderly)
Initially 30mg
daily, increased
to 60mg once
daily; may be
increased to 90120mg/daily
Initially
75mg/day; may
be increased to
max 225mg/day.
Dosage
increases can be
made at intervals
of 2 weeks or
more.
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
PD
Initially 10mg daily; increased
weekly in 10mg steps to a usual
maintenance dose of 40 mg
daily; (limited efficacy at higher
doses but some may require up
to 60mg daily; max 60mg
(40mg od in elderly)
OCD
Initially 20mg daily;
increased weekly in
10mg increments to
a usual
maintenance dose
of 40 mg daily;
(limited efficacy at
higher doses but
some may require
up to 60mg daily;
max 60mg
(40mg od in elderly)
Initially 37.5 mg/day for 7 days
increased to 75 mg/day. Further
increases can be made in 75mg
steps after at least 2 weeks to
max 225mg/day.
Updated: Jan 2017
Next Review: Jan 2019
SAD
Initially 20mg/day,
(limited efficacy at
higher doses)
further increases in
increments of 10
mg at intervals of
at least one week
to a maximum of
50mg/day (40mg
od in elderly)
Initially 75mg/day;
may be increased
to max 225mg/day.
Dosage increases
can be made at
intervals of 2
weeks or more.
21 |
PTSD
Initially
20mg/day,
(limited efficacy
at higher doses)
further increases
in increments of
10 mg at intervals
of at least one
week to a
maximum of
50mg/day (40mg
od in elderly)
Pharmacological Agents for Anxiety Disorders – Licensed Indications and Doses
Drug
Licensed
Indications
Amitriptyline
Depressive
illness
Clomipramine
Dose Recommendations
GAD
initially 75 mg (elderly
30–75mg) daily in divided
doses or as a single dose
at bedtime increased
gradually as necessary to
150–200mg
PD
OCD
SAD
Phobic and
obsessional
states
Depressive
illness
Initially 25 mg daily
(elderly 10 mg daily)
increased over 2 weeks
to 100–150 mg daily;
max. 250 mg daily
Initially 25 mg daily
(elderly 10 mg daily)
increased over 2
weeks to 100–
150 mg daily; max.
250 mg daily
Initially 25 mg daily
(elderly 10 mg
daily) increased
over 2 weeks to
100–150 mg daily;
max. 250 mg daily
Imipramine
Depressive
illness
Initially 10mg/day may be
increased gradually to 75
to 150mg/day; doses of
200mg daily may be
necessary
Elderly, lower doses - 30–
50 mg daily (Unlicenced)
Trazodone
Depression
including with
anxiety
Anxiety, 75 mg daily,
increasing as necessary
to 300 mg daily
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
22 |
PTSD
Pharmacological Agents for Anxiety Disorders – Licensed Indications and Doses
Drug
MAOIs
Licenced
Indications
Moclobemide
Social anxiety
disorder (SAD)
Depressive
illness
Phenelzine
Mixed anxiety
and depression
and phobic or
hypochondriacal
features
(Depression
characterised as
'atypical', 'non
endogenous',
'neurotic' or
where treatment
with other
antidepressants
has failed)
Dose Recommendations
GAD
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
PD
OCD
SAD
PTSD
Social anxiety disorder,
initially 300 mg daily
increased on fourth day to
600 mg daily in 2 divided
doses, continued for 8–12
weeks to assess efficacy
15mg three times
daily; if no response
after 2 weeks,
increase to 15 mg
four times daily;
severely depressed
patients in hospital
may be given up to
30mg three times
daily; then reduced
gradually to lowest
possible maintenance
dose (15 mg on
alternate days may
be adequate)
Updated: Jan 2017
Next Review: Jan 2019
15mg three times daily; if
no response after 2
weeks, increase to 15 mg
four times daily; severely
depressed patients in
hospital may be given up
to 30mg three times daily;
then reduced gradually to
lowest possible
maintenance dose (15 mg
on alternate days may be
adequate)
23 |
15mg three times
daily; if no
response after 2
weeks, increase
to 15 mg four
times daily;
severely
depressed
patients in
hospital may be
given up to 30mg
three times daily;
then reduced
gradually to
lowest possible
maintenance
dose (15 mg on
alternate days
may be
adequate)
Pharmacological Agents for Anxiety Disorders – Licensed Indications and Doses
Drug
Other
Licensed
Indications
Pregabalin
Generalised
Anxiety Disorder
(GAD) in adults
Dose Recommendations
GAD
Initially 150mg/day;
this may be
increased at weekly
intervals in steps of
150 mg, to a
maximum of 600 mg
daily
PD
OCD
SAD
Benzodiazepines
Diazepam
Short term use in
severe anxiety
Lorazepam
Short term use in
severe anxiety
Clonazepam
Not licenced for
anxiety
2mg 3 times daily,
increased if
necessary to 1530mg daily
1-4mg daily in
divided doses
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Initial oral dose of
250 micrograms
twice daily. This may
be increased after 3
days to a total of
1 mg daily
Updated: Jan 2017
Next Review: Jan 2019
24 |
PTSD
References
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McCrone P, Nabarro D, O’Neill C, Scott J, Wee N & Wittchen H-U (2014) Evidence-based pharmacological treatment of anxiety disorders, posttraumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for
Psychopharmacology. Journal of Psychopharmacology, 1-37 at: http://www.bap.org.uk/pdfs/AnxietyGuidelines2014.pdf
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Psychiatric Association, 2007. Guideline Watch March 2013. Available online at: http://psychiatryonline.org/guidelines
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Robert J. Ursano et al 2004. Guideline Watch added March 2009. Available online at: http://psychiatryonline.org/guidelines
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http://psychiatryonline.org/guidelines
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.
th
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disorder
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disorder
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
25 |
12. NICE Clinical Knowledge Summaries. Obsessive-compulsive disorder. Last revised in July 2013. http://cks.nice.org.uk/obsessive-compulsive-
disorder
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http://www.nice.org.uk/advice/ktt8/resources/non-guidance-firstchoice-antidepressant-use-in-adults-with-depression-or-generalised-anxietydisorder-pdf
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benzodiazepines-and-codeine
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http://www.mhra.gov.uk/Safetyinformation/Generalsafetyinformationandadvice/Product-specificinformationandadvice/Productspecificinformationandadvice%E2%80%93M%E2%80%93T/Selectiveserotoninreuptakeinhibitors/Informationforhealthcareprofessionals/index.htm#l3
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19. MHRA/CHM. Hydroxyzine: Risk of QT-interval prolongation and torsade de pointes. Drug Safety Update volume 8 issue 9 April 2015: 1.
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http://www.panmerseyapc.nhs.uk/guidelines/documents/G11.pdf
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https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/385791/PHENHS_England_pregabalin_and_gabapentin_advice_Dec_2014.pdf
Mersey Care Clinical Guideline / Formulary Document
Anxiety Disorders
Updated: Jan 2017
Next Review: Jan 2019
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