Low risk of sexual dysfunction versus placebo Incidence of sexual dysfunction (% of patients) Pregabalin (n=1149) Placebo (n=484) Libido decreased 2 1 Anorgasmia Abnormal ejaculation* 4 Impotence* 3 Treatment-emergent adverse events related to sexual dysfunction were very infrequent in pregabalin clinical trials Although the incidences of these adverse events in the pregabalin treatment group were slightly higher than placebo, they were very infrequent Reference Data on file – PGB023 (AE summary GAD) Pfizer Ltd. *Incidence in men. Data on file – PGB023 (AE summary GAD) Pfizer Ltd. LYG100 January 2009 1

Hepatically impaired patients Pregabalin may be useful due to renal clearance! Predominantly excreted unchanged in the urine Does not inhibit drug metabolism in vitro Is not bound to plasma proteins Hence unlikely to produce or subject to pharmacokinetic interactions

NICE Clinical Guideline 113 (January 2011) For patients: If antidepressants are not suitable for you, you may be offered pregabalin. For prescribers: 1.2.24. If the person cannot tolerate SSRIs or SNRIs, consider offering pregabalin.

Efficacy vs. effectiveness of benzodiazepines systematic review and meta-analysis of RCTs Withdrawals due to lack of efficacy Withdrawals for any reason Martin JLR et al. J Psychopharmacol 2007; 21: 774-782

% of patients receiving >1 year’s treatment by age

Withdrawal features with BZDs They have notorious reputation with the public Little or no dose escalation yet physical dependence Characteristic withdrawal syndrome (“sedative/alcohol”) - often bizarre symptoms - claims for prolonged syndrome Can be hazardous - fits, psychosis Poor outcome, especially in the elderly

BDZ’s (Not recommended by NICE for long term use!) May be needed In short term acute situations May be needed as adjunctive treatments with AD’s, anticonvulsants or psychological Treatments Issues are side effects (sedation and cognitive effects) and dependence in long term use Not as good for psychic symptoms (antidepressants better) More 3rd line after SSRI’s or Anticonvulsants and or psychological treatments Should be reserved and used in persistent, severe , disabling , refractory illnesses Regular not PRN Diazepam, Clonazepam (1-4mg) is better in chronic anxiety than Lorazepam, Alprazolam due longer half life and slower absorption so less dependence potential

If some one is already taking BDZ more than 4 times a week Start SSRI’s build it up to therapeutic doses in 4-6 weeks and continue for 12 weeks before attempting to withdraw If you get to a stage where you cannot get any further.. Substitute short acting drugs with long acting ones to make tapering easier! May need some Beta blockers/CBT at end stages of withdrawal Some patients may need both!

Azapirones in acute treatment of GAD efficacious in acute treatment especially if benzodiazepine-naïve P’s who have recently withdrawn from BDZ’s may suffer more symptoms as Buspirone has no effect on BDZ withdrawal syndrome less well tolerated than benzodiazepines and less effective than BDZ’s Chessick CA et al. Cochrane Database Syst Rev 2006; 3: CD006115