C.06.03 Pregabalin: the development programme and clinical data

P8 Other topics & Jacobi 2005). Patients present to their primary care physician with multiple physical symptoms. Despite high GAD incidence, few sufferers are diagnosed, prescribed medication, or receive psychiatric referral-simple diagnostic tools to aid patient recognition and monitoring are needed. Regardless of specific diagnosis, physicians require effective GAD-symptom treatments. CBT is an effective GAD treatment, showing equal/superior response rates to medication (Borkovec et al 2003). Benzodiazepines are rapidly effective, without long-term side effects, although concerns regarding discontinuation difficulties have limited usage. Buspirone, a partial agonist of 5-HT1A, has no discontinuation problems, but its efficacy is questionable. Most authorities recommend the safe and well-tolerated SSRIs/SNRIs as first-line GAD treatment. However, when given chronically, as required by many GAD patients, they may also cause adverse events (Gorman 2003). As well as increased CBT utilization, new molecular targets should be identified, including alpha-2-delta calcium ion channels (eg, pregabalin), glutamate receptor (eg, riluzole), CRF receptor, and 5-HT1A receptor (eg, full agonists).

References [1] Wittchen, HU et al. (1994). DSM-III-R generalized anxiety disorder in the National Comorbidity Smwey. Arch Gen Psychiatry. (51) 355 364. [2] Wittchen, HU and Jacobi, F (2005) The size and burden of mental disorders in Europe. Eur Neuropsychopharmacol. In press. Lieb, R et al (2005). The epidemiology of GAD in Europe. Eur Neuropsychopharmacol. In press.

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Pregabalin: the development programme and clinical data

S.A. Montgomery*. Imperial College, School of Medicine at St Maty "s Hospital, Department of Pharmacology, London, United Kingdom Pregabalin is currently available in the EU for the treatment of peripheral neuropathic pain, and for adjunctive treatment of partial seizures in epilepsy. It also shows efficacy in treating GAD. Pregabalin represents a new class of anxiolytic, with a different mechanism of action from all agents currently indicated for GAD management-it binds to the alpha-2-delta subunit of calcium channels, attenuating calcium influx into presynaptic terminals, thereby reducing excessive release of excitatory neurotransmitters (Fields et al 2001). In 5/6 short-term studies and 1 long-term relapse prevention study, pregabalin demonstrated consistent efficacy in treating GAD (Pohl et al 2005). Onset of action equivalent to alprazolam and faster than venlafaxine was seen by Week 1, as assessed by the HAM-A total score. Pregabalin showed equal psychic symptom treatment efficacy versus alprazolam and venlafaxine, but only pregabalin achieved greater improvement than placebo for somatic symptoms. Both the whole pregabalin safety database (n > 9000) and the GAD cohort (n 1149) show pregabalin to be well tolerated versus placebo; dizziness and somnolence were the most commonly reported adverse events (AEs). AEs frequently observed with SSRIs and the SNRI venlafaxine, eg, sexual dysfunction, were seen in very few pregabalin-treated patients. AEs were generally mild and transient, leading to low discontinuation rates (Rickels et al 2005). In conclusion, rapid onset of anxiolytic effect, and efficacy in treating psychic and somatic anxiety symptoms, were seen with pregabalin. Pregabalin was also safe and well tolerated. Therefore, pregabalin potentially offers physicians a novel therapy to optimize the treatment of GAD patients.

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References [1] Field, MJ et al. (2001). Pregabalin may represent a novel class of anxiolytic agents with broad spectrum of activity. Br J Pharmacol. 132(1):14. [2] Pohl, RB et al. (2005). Efficacy of pregabalin in the treatment of generalized anxiety disorder. Double-blind, placebo-controlled comparison of bid versus tid dosing. J Clin Psychopharmacol. In press. [3] Rickels, K et al. (2005). Pregabalin's persistent efficacy in the treatment of physical-somatic symptoms in outpatients with generalized anxiety disorder (GAD). ADAA, March 17 20, Seattle, WA.

C.07 Bipolar disorder: a multidimensional illness requiring a multifaceted approach Supported by an unrestricted educational grant from AstraZeneca

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Better understanding the use of the atypical antipsychotics in bipolar depression: informing clinical practice

J.R. Calabrese *. Case Western Reserve University, University Hospitals of Cleveland, Cleveland, USA Bipolar depression is the most prevalent and disabling phase of bipolar disorder with patients experiencing depressive symptoms 30 50% of the time, compared with <15% for manic, hypomanic or mixed symptoms. Depression causes greater disruption of occupational, family and social functioning than mania, and is associated with higher rates of morbidity and suicidality. Atypical antipsychotics are now established as an effective treatment option for bipolar mania and emerging data indicate that some agents may also be effective against bipolar depression. Studies have demonstrated the effectiveness ofrisperidone combination therapy (Vieta et al., 2001) and olanzapine combination therapy in the treatment of bipolar depression, though olanzapine monotherapy yielded only modest improvement in depressive symptoms (Tohen et al., 2003). More recently, the BOLDER I study examined the effectiveness of quetiapine monotherapy in bipolar depression. This 8-week, double-blind, randomised study of 511 patients with bipolar I or bipolar II depression demonstrated that both 300 and 600mg/day quetiapine monotherapy significantly improved levels of depression compared with placebo (effect sizes: 0.66 and 0.80, respectively). Furthermore, patients experienced significantly greater improvements in anxiety, sleep quality and quality of life compared with placebo (Calabrese et al., in press). Posthoc analyses of the BOLDER study will be presented showing the relationship between treatment response and baseline factors (eg levels of depression, anxiety, fatigue and the presence of rapid cycling). Additional data from the Quality of Life Enjoyment and Satisfaction Questionnaire and the Pittsburgh Sleep Quality Index will also be presented.

References [1] Calabrese, J.R., Keck JL:, P.E., Macfadden, W., Minkwitz, M., KetteL', T.A., Weisler, R.H., Cutler, A.J., McCoy, R.N., Wilson, E., Mullen, J., for the BOLDER Study Group. A randomized, doubleblind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am. J. Psychiatry, in press. [2] Tohen, M., Vieta, E., Calabrese, J., Ketter, T.A., Sachs, G., Bowden, C., Mitchell, RB., Centorfino, E, Risser, R., Baker, R.W., Evans, A.R., Beymer, K., Dube, S., Tollefson, G.D., Breier, A., 2003. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch. Gen. Psychiatry 60, 1079 1088. [3] Vieta, E., Goikolea, J.M., Corbella, B., Benabarre, A., Reinares, M., Martlnez, G., Fernfindez, A., Colom, E, Martlnez-Arfin, A., Torrent,