General anxiety disorder , treatment

Antidepressants are small heterocyclic molecules entering the circulation after oral administration and passing the blood-brain barrier to bind at numerous specific sites in the brain. They are used for treatment of depression, panic disorders, generalized anxiety disorder, social phobia, obsessive compulsive disorder, and other psychiatric disorders and nonpsychiatric states. 

Out-patient treatment is substantially cheaper than in-patient management and is generally as effective (Lowman, 1991). A French study on patients with generalized anxiety disorder estimated costs per patient over 3 months to he US 423 for hospitalization, 335 for out-patient services and 43 for medications (Souetre et al, 1994). Comorbid conditions (mostly alcoholism and depression) doubled these direct health-care costs. Over three-quarters of all patients were taking anxiolytic medication. 

Generalized anxiety disorder has been relatively neglected from the point of view of both health economics and pharmacoeconomics. The changing diagnostic criteria have made it difficult to compare data over time, leading researchers to focus on the more clearly defined disorders such as panic and obsessions. Drug treatment has been dominated by the benzodiazepines, usually available genetically and cheaply. However, as the final section of this chapter will show, all this is in flux. 

Benzodiazepines are recommended for acute treatment of generalized anxiety disorder when short-term relief is needed, as an adjunct during initiation of antidepressant therapy, or to improve sleep. 

Allgulander C, Bandelow B, Hollander E, et al. WCA recommendations for the long-term treatment of generalized anxiety disorder. CNS Spectrum 2003 8(8 Suppl 1) 53—61. 

In addition to treating MDD [51-53], duloxetine was approved as the first agent for the treatment of painful diabetic neuropathy in the U.S. [54-56]. It also has been used for stress urinary incontinence in women in Europe [57,58]. In 2007, duloxetine was approved for the treatment of generalized anxiety disorder in the U.S. 

Delle Chiaie, R., Pancheri, P., Casacchia, M., Stratta, P., Kotzalidis, G.D. and Zibellini, M. (1995) Assessment of the efficacy of buspirone in patients affected by generalized anxiety disorder, shifting to buspirone from prior treatment with lorazepam a placebo-controlled, doubleblind study. Journal of Clinical Psychopharmacology, 15,... 

Rickels K, Downing R, Schweizer E, Hassman H. (1993). Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam. Arch Gen Psychiatry. 50(11) 884-95. 

Generalized Sociai Anxiety Disorder, Treatment Resistance. A significant minority of patients will not experience a satisfactory treatment response to antidepressant therapy, even after a trial of adequate duration at full strength doses. For those with comorbid depression who are experiencing no benefit from SSRI treatment for either the anxiety or depression, then switching treatment is advisable. The options include switching to another SSRI, a SNRI (venlafaxine or perhaps dulox-etine), or, when other alternatives fail, phenelzine. 

Buspirone. A nonbenzodiazepine anxiolytic, buspirone is an effective treatment for generalized anxiety disorder but not other anxiety disorders. There are as yet no published controlled studies of buspirone for PTSD, though a small open label series suggested it might be effective for the core symptoms of PTSD. In the absence of more definitive evidence regarding its effectiveness, we do not routinely use buspirone when treating PTSD. 

Rynn MA, Brawman-Mintzer O. Generalized anxiety disorder acute and chronic treatment. 

Anxiety Treatment of generalized anxiety disorder (GAD) and social anxiety disorder (SAD) (extended-release [ER] only). 

In recent years many of these primary care cases that would formerly have been seen as anxiety disorders have been portrayed as anxious-depressives and have led to treatment with antidepressants, in particular the more recent serotonin reuptake inhibitors. As part of this rebranding a variety of states such as panic disorder, post-traumatic stress disorder, social phobia and generalized anxiety disorder have appeared, along with more traditional disorders such as obsessive compulsive disorder (OCD). Many of these diagnoses are likely to lead to prescriptions of an SSRI although the evidence for benefit from SSRIs is poor except for OCD. 

Allgulander C, Hackett D, Salinas E (2001) Venlafaxine extended release (ER) in the treatment of generalized anxiety disorder twenty-four-week placebo-controlled doseranging study. Br J Psychiatry 179 15-22... 

Enkelmann R (1991) Alprazolam versus buspirone in the treatment of outpatients with generalized anxiety disorder. Psychopharmacology (Berl) 105 428-432 Faravelli C, Rosi S, Truglia E (2003) Treatments benzodiazepines. In Nutt DJ, BaUenger JC (eds) Anxiety disorders. Blackwell Science, Oxford, pp 315-338 Fawcett J, Barkin RL (1998) A meta-analysis of eight randomized, double-blind, controlled clinical trials of mirtazapine for the treatment of patients with major depression and symptoms of anxiety. J Clin Psychiatry 59 123-127 Febbraro GA, Clum GA (1998) Meta-analytic investigation of the effectiveness of self-regulatory components in the treatment of adult problem behaviors. Clin Psychol Rev 18 143-161... 

Ferreri M, Hantouche EG (1998) Recent clinical trials of hydroxyzine in generalized anxiety disorder. Acta Psychiatr Scand 393 Suppl 102-108 Foa EB (2000) Psychosocial treatment of posttraumatic stress disorder. J Clin Psychiatry 61 Suppl 5 43-48... 

Dunn R, Reed TA, Copeland PD, Frye CA (1998) The nitric oxide synthase inhibitor 7-nitroindazole displays enhanced anxiolytic efficacy without tolerance in rats following subchronic administration. Neuropharmacology 37 899-904 Freeman AR, Westphal J, Norris G, Roggero B, Webb P, Freeman K (1997) Efficacy of ondansetron in the treatment of generalized anxiety disorder. Depress Anxiety 5 140-141... 

The selective serotonin reuptake inhibitors (SSRI) have been used in adults for a wide variety of disorders, including major depression, social anxiety (social phobia), generalized anxiety disorder (GAD), eating disorders, premenstrual dysphoric disorder (PMDD), post-traumatic stress disorder (PTSD), panic, obsessive-compulsive disorder (OCD), trichotillomania, and migraine headaches. Some of the specific SSRI agents have an approved indication in adults for some of these disorders, as reviewed later in this chapter. The SSRIs have also been tried in children and in adults for symptomatic treatment of pain syndromes, aggressive or irritable ( short fuse ) behavior, and for self-injurious and repetitive behaviors. This chapter will review general aspects of the SSRIs and discuss their approved indications in children and adolescents. 

Rynn, M.A., Siqueland, L., and Rickels, K. (2001) Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder. Am J Psychiatry 158 2008-2014. 

Rynn, M. A., and O. Brawman-Mintzer. Generalized Anxiety Disorder Acute and Chronic Treatment. CNS Spectr. 9(10) (2004) 716-23. 

---