Anxious patients

Inadequate activity of an endogenous ligand which is a benzodiazepine receptor agonist and suppresses anxiety. In this case, the administration of the antagonist, fiumazenil, should induce anxiety in normal subjects and exacerbate anxiety in anxious patients. 

Dysfunction of the GABAa receptor complex such that the effects of all benzodiazepine receptor ligands are shifted in the direction of inverse agonism. In this case, fiumazenil (which normally has zero efficacy) should induce anxiety in anxious patients but have no effects in healthy subjects because they have normal receptors. 

Evaluation of the anxious patient requires a complete physical and mental status examination appropriate laboratory tests and a medical, psychiatric, and drug history. 

Initially, anxious patients should be monitored once to twice weekly for reduction in anxiety symptoms, improvement in functioning, and side effects. The Visual Analog Scale may assist in the evaluation of drug response. 

Optimal treatment of an anxious patient involves far more than the prescription of medication (Fig. 1). The skill of the psychiatrist in establishing the... 

The effect of increased cardiac output on the administered dose of anesthetic is opposite that discussed for reduced cardiac output. Intensely anxious patients and those who have such diseases as thyrotoxicosis usually require larger doses of anesthetic to induce anesthesia. 

Therapeutic response, characterized by a calm facial expression and decreased restlessness in anxious patients and a decrease in intensity or frequency of seizures in patients with seizure disorder... 

Cox BJ, Hasey G, Swinson RP, et al. The symptom structure of panic attacks in depressed and anxious patients. Can J Psychiatry 38 181-184, 1993b... 

Thyrer BA, Parrish RT, Himle J, et al Alcohol abuse among clinically anxious patients. Behav Res Ther 24 357-359, 1986... 

Unlike benzodiazepines, buspirone is not associated with sedative or abuse problems, but some clinicians have observed that bus-pirone s anxiolytic properties do not appear to be as potent as those of benzodiazepines, particularly in patients who have previously received a benzodiazepine. Because buspirone is not sedating and has no psychomotor effects, it has a distinct advantage over benzodiazepines when optimal alertness and motor performance are necessary. Response to buspirone occurs in approximately 2-4 weeks. Buspirone does not show cross-tolerance with benzodiazepines and other sedative or hypnotic drugs such as alcohol, barbiturates, and chloral hydrate. Therefore, buspirone does not suppress benzodiazepine withdrawal symptoms. In anxious patients who are taking a benzodiazepine and who require a switch to buspirone, the benzodiazepine must be tapered gradually to avoid withdrawal symptoms, despite the fact that the patient is receiving buspirone. 

Because long-term exposure to high-dose benzodiazepines may place some patients at risk for physical and psychological dependence, we recommend the use of antidepressants for the treatment of panic disorder. For most patients, SSRIs should be considered first-line agents. The choice should be based on the factors discussed in Chapter 2. MAOls are usually reserved for patients whose symptoms have not responded to SSRIs and TCAs. A major caveat is that patients with panic disorder initially may be highly sensitive to the stimulant effect of small doses of antidepressants. For highly anxious patients with panic disorder, treatment may be... 

American Psychiatric Association Benzodiazepine Dependence, Toxicity, and Abuse A Task Force Report of the American Psychiatric Association. Washington, DC, American Psychiatric Association, 1990 Cohn JB, Wilcox CS Low-sedation potential of buspirone compared with alprazolam and lorazepam in the treatment of anxious patients a double-blind study. J Clin Psychiatry 47 409 12, 1986 Dolovich LR, Addis A, Vaillancourt JM, et al Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and case-control studies. BMJ 317 839-843, 1998 Goldberg HL, Finnerty RJ The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry 136 1184—1187, 1979 Kupfer DJ, Reynolds CF 111 Management of insomnia. N Engl J Med 336 341-346, 1997... 

Clinical studies have also found that anxious patients treated for up to 12 months are able to stop treatment abruptly without withdrawal symptoms ( 34, 50). 

Two studies have indicated that the tricyclic antidepressant (TCA) imipramine may be as effective as BZDs in the treatment of GAD ( 58, 59). No studies longer than 8 weeks duration have been conducted, however, and imipramine s onset of anxiolytic action may be even slower than that of buspirone. Aithough adverse effects also may limit usefulness, its lack of dependence liability may make it an appropriate alternative in chronically anxious patients who also suffer from panic and depression. 

Despite very limited efficacy in most anxious patients, b-blockers may be useful for highly somatic individuals, such as those with performance anxiety. Antihistamines... 

Rickels K, Case G, Downing R, et al. One-year follow-up of anxious patients treated with diazepam. J Clin Psychopharmacol 1986 6 32-36. 

Fontaine R, Chouinard G, Annable L. Rebound anxiety in anxious patients after abrupt withdrawal of benzodiazepine treatment. Am J Psychiatry 1984 141 848-852. 

At present, SSRIs are the most commonly prescribed first-line agents in the treatment of both MDD and anxiety disorders. Their popularity comes from their ease of use, tolerability, and safety in overdose. The starting dose of the SSRIs is usually the same as the therapeutic dose for most patients, and so titration may not be required. In addition, most SSRIs are now generically available and inexpensive. Other agents, including the SNRIs, bupropion, and mirtazapine, are also reasonable first-line agents for the treatment of MDD. Bupropion, mirtazapine, and nefazodone are the antidepressants with the least association with sexual side effects and are often prescribed for this reason. However, bupropion is not thought to be effective in the treatment of the anxiety disorders and may be poorly tolerated in anxious patients. The... 

The role of ChCMs as anxiolytic agents has not been extensively investigated. Clinical data have shown reduced anxiety in smokers and decreased anxiety induced by a stress-producing movie.77 With many patients suffering from anxiety, there is a concurrent overlap of depression, where two thirds of patients diagnosed with depression are anxious and almost all anxious patients will encounter an episode of depression.78 Benzodiazepines, such as diazepam, have long been the treatment of choice for anxiety. However, they are depressants and therefore could contribute to the depression in many patients, thereby limiting their use. 

Three types of endozapines have been isolated. It is known that the beta-carbolines can be synthesized in the mammalian brain and that, in vitro, they act as inverse agonists at benzodiazepine receptor sites. Theoretically such compounds could induce anxiety. However, none of these compounds has been isolated in vivo and the original detection of a beta-carboline in the urine of anxious patients was later found to be an artifact, possibly caused by bacterial contamination. 

Because of its virtual absence of respiratory depressant effects compared with benzodiazepines (20), buspirone may be especially useful in treating anxious patients with lung disease (21). 

Usually, anxious patients tend to be more sensitive to and less tolerant of side effects of all kinds, particularly those associated with the stimulation effects of SSRI treatment. In the short term, the medication may actually make the anxiety worse rather than better. The physician will usually select a less stimulating SSRI and typically will begin treatment with a very low dose, increasing it gradually. 

Noradrenergic model. This model suggests that the autonomic nervous system of anxious patients is hypersensitive and overreacts to various stimuli. The locus ceruleus may have a role in regulating anxiety, as it activates norepinephrine release and stimulates the sympathetic and parasympathetic nervous systems. Chronic noradrenergic overactivity down regulates 02-adrenoreceptors in patients with generalized anxiety disorder (GAD) and posttraumatic stress disorder (PTSD). Patients with social anxiety disorder (SAD) appear to have a hyperresponsive adrenocortical response to psychological stress. 

Alprazolam XR may be dosed less frequently than immediate release alprazolam, and lead to less inter-dose breakthrough symptoms and less clockwatching in anxious patients... 

Benzodiazepines for jItterIness and anxiety, especially at Initiation of treatment and especially for anxious patients... 

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