Anxiety disorders effectiveness

The definition of desired therapeutic and side effects in the case of the benzodiazepines very much depends on the clinical problem in question. The sedative and hypnotic actions are desired effects in the treatment of insomnia, but undesired effects in the treatment of anxiety disorders. Effects that are usually undesired include daytime drowsiness, potentiation of the sedative effects of ethanol, and anterograde amnesia. They are mediated via the benzodiazepine site of GABAa receptors, since they can be antagonized with flumazenil. 

Charney, D.S., Woods, S.W., Heninger, G.R. Noradrenergic function in generalized anxiety disorder effects of yohimbine in healthy subjects and patients with generalized anxiety disorder. Psychiatry Res. 27(2), 173—182, 1989. 

Belanger L, Morin CM, Langlois F, Ladouceur R (2004) Insomnia and generalized anxiety disorder effects of cognitive behavior therapy for gad on insomnia symptoms. J Anxiety Disord 18 561-571... 

Anxiolytics are drugs used for the treatment of anxiety disorders. Apart from benzodiazpines, a frequently used anxiolytic is the 5HT1A (serotonin) receptor agonist buspiron, which has no sedative, amnestic or muscle-relaxant side effects, but whose action takes about a week to develop. Furthermore, it is less efficaceous than the benzodiazepines. Buspiron s mechanism of action is not fully understood. 

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

Lejoyeux et al. 1998). Similar to opioid-dependent persons, these patients reported that they use benzodiazepines to self-medicate anxiety, insomnia, and alcohol withdrawal and, less commonly, to enhance the effects of ethanol. Approximately l6%-25% of patients presenting for treatment of anxiety disorders abuse alcohol (Kushner et al. 1990 Otto et al. 1992). Controversy exists concerning appropriate benzodiazepine prescribing in this population (Cir-aulo and Nace 2000 Posternak and Mueller 2001). 

Pharmacodynamic tolerance to the psychomotor effects of benzodiazepines has been demonstrated after single or multiple doses (File 1985 Greenblatt and Shader 1978 Rosenberg and Chiu 1985). Pharmacodynamic tolerance to the anxiolytic effect (over a 6-month period) has not been demonstrated (Rickels et al. 1983), and clinical experience supports the view that many patients with anxiety disorders require long-term therapy with benzodiazepines or alternative antianxiety agents. An important clinical consequence of tolerance to sedative effects is observed in benzodiazepine overdoses, when patients may initially be... 

Fyer AJ, Liebowitz MR, Gorman JM, et al Effects of clonidine on alprazolam discontinuation in panic patients a pilot study. J Clin Psychopharmacol 8 270—274,1988 Garvey MJ, Tollefson GD Prevalence of misuse of prescribed benzodiazepines in patients with primary anxiety disorder or major depression. Am J Psychiatry 143 1601-1603, 1986... 

Shah and Jenkins (2000) in a review of mental health economic studies from around the world identified 40 cost-of-illness studies, of which five covered all disorders, one neuroses, two panic disorders and one anxiety. All were from developed countries. There were numerous cost-effectiveness studies but none involving the anxiety disorders specifically. One study in the UK examined the cost-benefit analysis of a controlled trial of nurse therapy for neurosis in primary care (Ginsberg et al, 1984). 

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. 

The pharmacoeconomics of the anxiety disorders has received litde attention. In the past drug costs were largely incurred by use of benzodiazepines, most of which are available in generic forms and are cheap. They are effective and acceptable in the short term. Long-term use is associated with the risk of physical dependence, with an adverse risk—benefit ratio and high cost terms to facilitate withdrawal. There is now a trend towards the use of antidepressants in the anxiety disorders. Clinical experience has been followed by formal trial evaluation. 

Tricyclic antidepressants are not licensed for use in the anxiety disorders, so in theory the SSRIs should not be compared with them in cost-effectiveness terms. The SSRIs and venlafaxine are supplanting benzodiazepines as the latter s long-term problems become more appreciated. The SSRIs will take an increasing proportion of the market. However, in comparison with the overall costs of the anxiety disorders, this drug expenditure can be justified. Further cost-offset and cost-effectiveness studies will help hammer this point home. 

Figure 19.8 A schematic representation of the GABAa receptor shift hypothesis. This proposes that patients with panic disorder have dysfunctional GABAa receptors such that the actions of drugs that behave as antagonists in normal subjects are expressed as inverse agonism in panic patients. It is unlikely that this theory extends to generalised anxiety disorder (GAD), for which benzodiazepine agonists are highly effective treatments, but it could explain why these drugs are relatively ineffective at treating panic disorder. (Based on Nutt et al. 1990)...

Panic disorder patients are more likely to experience stimulantlike side effects than patients with major depression and should be initiated on lower doses of antidepressant than those that are used for depression or other anxiety disorders. 

Several neuropeptides are under current investigation for their role in anxiety disorders. Important neuropeptides include neuropeptide Y (NPY), substance P, and cholecystokinin. NPY appears to have a role in reducing the effect of stress hormones and inhibiting activity of the LC. Both mechanisms may contribute to the anxiolytic properties seen experimentally. Substance P may have anxiolytic and antidepressant properties. This may be due in part to its effects on corticotropin-releasing hormone.21... 

Stimulants theoretically exert their effect by blocking the reuptake of dopamine and norepinephrine, thus improving academic performance and decreasing motor activity in ADHD patients. Stimulants have been shown to decrease fidgeting and finger tapping, increase on-task classroom behavior and positive interactions at home and in social environments, and ameliorate conduct and anxiety disorders.14... 

---