Portfolio
Medicines Management
Document name:
Pregabalin Communication
Document type:
Pharmacy / Prescribing Communication
Staff group to whom it applies: All prescribers, pharmacy and clinical staff
within the Trust
Distribution:
Trustwide
How to access:
Intranet
Issue date:
February 2014
Next review:
January 2016
Approved by:
Drug & Therapeutic Sub Committee
Developed by:
Mark Payne, Senior Clinical Pharmacist
Director leads:
Dr Booya, Medical Director
Contact for advice:
Medicines Information
Med.information@swyt.nhs.uk
Drug and Therapeutics Policy Action Group
Communication
Pregabalin for Generalised Anxiety Disorder (GAD)
Introduction
Pregabalin (Lyrica®, Pfizer) has been available in the Trust to prescribe as third line therapy for
generalised anxiety disorder or for when the individual cannot tolerate SSRIs or SNRIs in line with
current NICE guidance. Pregabalin has demonstrated equivalent efficacy to antidepressants for the
treatment of GAD but is significantly more expensive, especially when prescribed as TDS dosing.
Cost comparison
Pregabalin has a flat pricing structure i.e. all capsules have the same cost irrespective of strength.
This makes the following doses cost equivalent at £64.40 per month:
25mg BD / 50mg BD / 75mg BD / 100mg BD / 150mg BD / 200mg BD / 300mg BD
Using alternative doses / dosing regimens is significantly more expensive and so should only be done
where there is a clearly documented benefit from using an alternative dose / regimen.
For the same cost you can treat 20 patients with 60mg Fluoxetine, 6 patients with 200mg Sertraline or
2 patients with 225mg Venlafaxine XL.
Pharmacology / Clinical effectiveness
Pregabalin is an analogue of the mammalian neurotransmitter gamma-aminobutyric acid (GABA), and
decreases central neuronal excitability by binding to an auxiliary subunit (α2-δ protein) of a voltagegated calcium channel on neurons in the central nervous system.
Pregabalin has been studied in 6 controlled trials of 4-6 week duration, an 8 week study in older adults
and a long-term relapse prevention study totalling 12 months duration. Relief of the symptoms of GAD
as reflected by the Hamilton Anxiety Rating Scale (HAM-A) was observed by Week 1 (when dosed in
accordance with the guidance below), with continued improvement up to 6 weeks post-initiation, and
evidence that those who respond in the short term maintain this response up to 1 year.
In controlled clinical trials (4-8 week duration) 52% of the pregabalin treated patients and 38% of the
patients on placebo had at least a 50% improvement in HAM-A total score from baseline to endpoint,
this is comparable with the effects seen with antidepressants when used for the treatment of anxiety.
Dosage and administration
Pregabalin is renally excreted, so renal function must be assessed prior to initiation / review of dosing.
Dosing should be based on renal function as follows:
Creatinine clearance
(CLcr) (mL/min)
Total pregabalin daily dose
(To be given in divided doses)
Dose regimen
Starting dose (mg/day)
Maximum dose (mg/day)
≥ 60
150
600
BD
≥30 - <60
75
300
BD
≥15 - <30
25 – 50
150
Once Daily or BD
< 15
25
75
Once Daily
NB: there is no evidence of additional benefit for doses >450mg (in patients with Clcr >60)
Contra indications
Hypersensitivity to the active substance or constituents.
Adverse events and special precautions
The most commonly reported adverse reactions are dizziness and somnolence. Other common side
effects include: increased appetite, euphoric mood, confusion, irritability, libido decreased,
disorientation, insomnia, ataxia, coordination abnormal, tremor, dysarthria, memory impairment,
disturbance in attention, paraesthesia, sedation, balance disorder, lethargy, headache, blurred vision,
diplopia, vertigo, erectile dysfunction, vomiting, dry mouth, constipation, flatulence, gait abnormal,
feeling drunk, fatigue, oedema peripheral, oedema and weight gain.
Adverse reactions are usually mild to moderate in intensity. In all controlled studies, the
discontinuation rate due to adverse reactions was 12% for patients receiving pregabalin and 5% for
patients receiving placebo.
Discontinuation reactions with pregabalin are rare and occur at roughly the same rate as placebo for
all doses except those at 600mg/day.
Clinically relevant interactions
There have been no clinically important interactions between pregabalin and other medical products
reported, and due to its primary renal excretion it is unlikely that it will have a significant interaction
with any newly emerging treatments.
In common with other CNS depressant medications it is likely that when pregabalin is used in
combination with other CNS depressants that there is an additive sedative effect which may impact on
the ability to perform tasks, when used alongside alcohol there is an increased risk of death due to
respiratory depression.
Recommendations
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Pregabalin should be reserved for third-line treatment of GAD. It is useful in patients where the
side effects of antidepressants have limited their utility.
When prescribing pregabalin use twice daily administration unless renal function tests indicate
less frequent administration. Although three-times-daily administration is licensed, evidence
from trials indicates that this is no more effective than twice-daily administration and is 50%
more expensive.
Information from dose ranging studies indicates that the most effective and well tolerated
doses are between 200 and 450mg/day, doses up to 600mg/day are licensed but have not
demonstrated superior efficacy, but may be more difficult to stop.
Assess efficacy at 1 week post-initiation / dose adjustment, and consider that this is unlikely to
be the maximum effect seen from the prescribed dose. In on-going treatment assess efficacy
at 1 year post-initiation and consider the clinical risk / benefit of continuing treatment.
There is emerging evidence that there is now a risk of abuse / diversion with this medication
so any requests for additional supplies of medication should be monitored closely particularly
in those service users with a known history of substance misuse.
References
Montgomery S et al. (2012) Long term study of pregabalin for the treatment of generalized anxiety disorder: a 1 year
open-label extension. European Psychiatry. 27(S1): 1.
National Institute for Clinical Excellence. (2011) CG113: Anxiety.
Pregabalin SmPC, accessed at www.medicines.org.uk, Jan 2014
Rickels K et al.(2005) Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind,
placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiatry. 62(9):1022-30.