Cognitive behavioural therapy and pharmacotherapy: complementary or contradictory approaches to the treatment of anxiety?

Considerable controversy exists regarding the practice of combining Cognitive Behavioural Therapy (CBT) with Pharmacotherapy (PT) in the management of anxiety. This paper considers whether these two forms of treating anxiety disorders can be effectively combined to enhance treatment outcome. Despite the theoretical appeal of a combined approach, a critical review of treatment outcome findings across CBT and various anxiolytic medications and their combination, suggests a failure of these treatments to operate in a complementary fashion. A detrimental impact of anxiolytic medication on CBT outcome is particularly salient for high potency benzodiazepines. Low potency benzodiazepines and antidepressants generally have a negligible impact with no clear evidence of treatment enhancement and some negative combined treatment effects on medication withdrawal and at long-term follow-up. Thus, we address potential mechanisms that may explain this treatment noncomplementarity and in some cases, treatment incompatibility. Cognitive factors influencing treatment outcome (catastrophic beliefs, self-efficacy, selective attention, and memory) are highlighted in view of the empirically supported mediating role of these variables in accounting for treatment responsiveness. Potential effects of anxiolytic medication on cognitive change in CBT are postulated. A number of suggestions for future research and clinical practice are proposed on the basis of this review.     

Use and abuse of the benzodiazepines

Since chlordiazepoxide was introduced in 1961, the benzodiazepines have had many important roles in the pharmacotherapy of various disorders. This drug class for the central nervous system has been considered one of the safest in use for 35 years, especially when the benzodiazepines are compared with the barbiturates they often replaced. The objective of this article is to provide an update on the availability and distribution of benzodiazepines around the world and to discuss their most common clinical applications. Adverse effects of benzodiazepines, observed after long-term therapeutic use and after overdoses, are also presented. Triazolam is discussed because this benzodiazepine was removed from the market by regulatory authorities in the United Kingdom in 1991. Benzodiazepines will continue to have an important role in clinical medicine. Their clinical use, however, should be monitored more closely because of the greater awareness of their adverse effects after long-term use and because of the potential for misuse and abuse.     

"Interpreting in the dark": Race and ethnicity in psychoanalytic psychotherapy.

Discusses the impact of race and ethnicity on the psychotherapeutic process of 3 patients in psychoanalytic psychotherapy with an African-American therapist. Race and ethnicity remain topics that engender anxiety in social and clinical discourse. Psychoanalytic literature on race has been hampered by incomplete conceptualizations and overgeneralizations that often limit its clinical utility. Clinical examples are used to explore the way in which attention directed at racial issues provides a framework for the treatment alliance and illuminates key transferences and resistances. Discussion of racial issues is most fruitful when racial themes are situated in bodily and social contexts and when the meaning that race has in the therapy dyad is negotiated by patient and therapist, apart from idealized or socially correct conceptualizations from outside of the treatment situation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Animal models of anxiety: an ethological perspective

In the field of anxiety research, animal models are used as screening tools in the search for compounds with therapeutic potential and as simulations for research on mechanism underlying emotional behaviour. However, a solely pharmacological approach to the validation of such tests has resulted in distinct problems with their applicability to systems other than those involving the benzodiazepine/GABAA receptor complex. In this context, recent developments in our understanding of mammalian defensive behaviour have not only prompted the development of new models but also attempts to refine existing ones. The present review focuses on the application of ethological techniques to one of the most widely used animal models of anxiety, the elevated plus-maze paradigm. This fresh approach to an established test has revealed a hitherto unrecognized multidimensionality to plus-maze behaviour and, as it yields comprehensive behavioural profiles, has many advantages over conventional methodology. This assertion is supported by reference to recent work on the effects of diverse manipulations including psychosocial stress, benzodiazepines, GABA receptor ligands, neurosteroids, 5-HT1A receptor ligands, and panicolytic/panicogenic agents. On the basis of this review, it is suggested that other models of anxiety may well benefit from greater attention to behavioural detail.     

Pharmacologic treatments effective in both generalized anxiety disorder and major depressive disorder: clinical and theoretical implications

OBJECTIVE: To review the efficacy of anxiolytics (alprazolam and azapirones) in major depressive disorder (MDD) and that of antidepressants in generalized anxiety disorder (GAD), thereby exploring the possible theoretical and clinical implications of this efficacy. METHOD: A Medline literature search was performed for the period January 1980 to September 1997 of randomized, double-blind comparison studies between anxiolytics and antidepressants in the acute treatment of adult patients with either MDD or GAD. RESULTS: Alprazolam, at doses double those generally recommended for anxiety disorders, appears to be as effective as tricyclic antidepressants (TCAs) in the acute treatment of mild to moderate MDD. Alprazolam was also found to have a more rapid onset of action than to TCAs, particularly for the improvement of anxiety, somatization, and insomnia. Two azapirones (buspirone and gepirone) also have demonstrated a modest acute antidepressant effect in preliminary studies, albeit only in a depressed outpatient sample with considerable anxiety at baseline. Finally, various antidepressant drugs (imipramine, trazodone, paroxetine) were shown to have, at the least, comparable efficacy to benzodiazepines (BZDs) in the acute treatment of GAD. CONCLUSIONS: The nonspecificity of treatment response suggests that GAD and MDD are 1) different expressions of a similar disorder with a common neurobiological substrate, 2) discrete diagnostic entities that respond to independent pharmacological effects of the same drugs, or 3) a combination of the two (heterogeneity hypothesis). The most relevant clinical finding is the efficacy of antidepressants in the acute treatment of GAD.     

Comorbid anxiety disorders in late-life depression

We examined the prevalence and correlates of comorbid anxiety disorders in two groups of older depressed patients assessed at the University of Pittsburgh. A total of 336 older outpatients and inpatients with major depression were comprehensively evaluated with several instruments including the Hamilton Depression Rating Scale, and either the SADS-L or the SCID for DSM-III-R. These patients presented with major depression, associated with a wide range of functional, cognitive, and medical impairment. One-third to one-half of them also presented with severe symptomatic anxiety. However, only a small proportion (less than 5%) met diagnostic criteria for lifetime or current panic, obsessive-compulsive, or phobic disorders. At baseline, lifetime comorbid anxiety disorders were associated with a higher rate of alcoholism and higher symptomatic anxiety. Lifetime comorbid anxiety disorders did not affect the rate of response of depression, but they were associated with a higher use of benzodiazepines and a 50% increase in the time outpatients needed to respond. These findings suggest that, even in psychiatric patients with major depression, the lifetime prevalence of anxiety disorders is lower in late life, but that it has important clinical and therapeutic implications.     

Anesthetic considerations in the child with Gaucher disease

Alpidem, an imidazopyridine that acts at the gamma-aminobutyric acid/benzodiazepine receptor complex, has been reported to be an effective anxiolytic with a more favorable side effect profile than benzodiazepines. The effect of alpidem was investigated in an 8-week, open, clinical trial in 13 patients with panic disorder, with or without agoraphobia. Three patients were responders (much improved or very much improved), five patients were nonresponders, and five patients dropped out after less than 6 weeks of treatment. Significant improvement was seen in the sample as a whole for spontaneous panic attacks, phobic avoidance, and anticipatory anxiety. Most improvement occurred during the first 4 weeks of treatment, and responders had milder panic disorder at baseline. Adverse effects were generally mild. After 8 weeks of treatment, taper of medication over 2 weeks occurred without significant worsening of panic disorder symptoms. The efficacy of alpidem in the treatment of panic disorder remains uncertain and requires assessment in a controlled trial.     

Long-term treatment with abecarnil does not induce diazepam-like dependence in mice

Abecarnil (isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate) is a metabolically stable anxiolytic and anticonvulsant beta-carboline derivative with few sedative and muscle relaxant effects in rodents. Abecamil binds with high affinity to benzodiazepine receptors. Because long-term treatment with benzodiazepines leads to development of dependence, we evaluated in mice whether abecarnil also possesses a potential for producing dependence, using electroencephalographic and electromyographic monitoring, and behavioral assessment of anxiety to detect withdrawal responses after chronic treatment. Diazepam was used as a reference. Mice withdrawn from chronic treatment with diazepam (15 mg/kg/day for 12 days) showed a time-related evolution of anxiety, muscle rigidity and seizures between days 4 and 21 after discontinuation of the treatment. A period between withdrawal days 1 and 3 was symptom free. Mice withdrawn from chronic administration of abecarnil (6 mg/kg/day for 12 days) showed no anxiety and no changes in seizure susceptibility and muscle tone. The doses of diazepam and abecarnil used for chronic treatment were equivalent in terms of kinetics and binding to benzodiazepine receptors. These data indicate that long-term treatment with abecarnil does not induce benzodiazepine-like dependence in mice. Thus, it may be predicted that chronic treatment with abecarnil in humans may offer an important alternative to benzodiazepines in the treatment of anxiety.     

Psychotropic drugs and behavior

Behavioural modifications induced by psychotropic drugs results primarily from their pharmacological properties. According to classification of psychotropic drugs, sedative compounds contrast with psychostimulating medications. Behavioural effects of psychotropic drugs depend on dosing, subject's status (patient or healthy volunteer), acute or chronic administration, and environment. Some psychotropic compounds, particularly sedative drugs, decrease the level of mental alertness and cognitive functioning. But those deleterious effects tend to disappear during the course of a repeated administration. Some psychotropic drugs, especially benzodiazepines, induce a tolerance effect, eventually a psychic or a physiological dependence state evidenced by withdrawal reactions. Such similar dependence processes have been reported with other psychotropic drugs. Forensic problems have been attributed to some psychotropic compounds, like benzodiazepines: paradoxical aggressive reactions, psychomotor automatism; Psychotropic drugs usually can confer a positive effect on behaviour owing to their therapeutic action by the way of improving the illness and consequently the life of patients in the cases of depression, anxiety or schizophrenia.     

Observations on the cognitive behavioral treatment of panic disorder: Impact of benzodiazepines.

Examines whether or not benzodiazepines (BZDs) in general and alprazolam (ALP) in particular have a beneficial or negative impact on Cognitive Behavior Therapy (CBT). A survey of 2 panic disorder (PD) clinics revealed that approximately one-half of all PD patients receive combined treatment (usually CBT plus ALP). This strategy is the recommended treatment of choice for many. The rationale for such a treatment is that BZDs help to decrease anxiety and panic in the short run, making the patient amenable to psychotherapy, while CBT offers a long-term solution for coping with panic. However, the authors find that the concomitant use of BZDs throughout the course of CBT has an adverse effect on the psychotherapy. For CBT to be effective, anxiety must be elicited under the controlled circumstances of the therapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pharmacologic treatment for children and adolescents with anxiety disorders

Pediatric anxiety disorders are common illnesses that, if left untreated, may induce academic, family, and interpersonal problems. Cognitive-behavioral techniques and other psychotherapeutic interventions may be adequate for the treatment of most anxiety disorders. For patients with severe symptoms or for whom psychotherapeutic approaches are not adequate, medications are indicated. Among the available medications, the SSRIs are currently the first choice; however, other medications, such as the benzodiazepines and the TCAs, may be used alone or sometimes in combination with the SSRIs. Caution with respect to medication interactions and side effects is indicated. In particular, long-term side effects in these medications have not been well studied.     

Do People Need Self-Esteem? Comment on Pyszczynski et al. (2004).

In spite of impressive empirical evidence consistent with aspects of terror management theory (TMT) reviewed by T. Pyszczynski, J. Greenberg, S. Solomon, J. Arndt, and J. Schimel (2004), several fundamental assumptions of the theory remain untested or lack support. Specifically, Pyszczynski et al. (2004) have not demonstrated that (a) people need self-esteem, (b) pursuing self-esteem is an effective means for reducing anxiety, (c) pursuing self-esteem helps people achieve their important goals, (d) having or pursuing self-esteem is the only way to deal with anxiety to achieve important goals, or (e) death is the real issue driving the pursuit of self-esteem. The authors suggest there is a different paradigm for thinking about death, one in which awareness of one's mortality serves as a precious reminder of the limited time one has to accomplish one's most important goals. All of these questions can be addressed with empirical research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulus generalization as a function of clinical anxiety.

"It was hypothesized that the state inferred from manifest clinical symptoms of anxiety would show functionally similar motivational properties to the state of anxiety defined in terms of an implicit response that has been conditioned to situations involving noxious stimulation. It was predicted that both types of anxiety would exhibit the energizing properties of a drive and therefore elevate response gradients of generalization… . The results showed that the groups designated as high in clinical anxiety showed significantly more generalization than the low-clinical anxiety groups under the strong-shock condition. No difference was found between the 2 levels of clinical anxiety for either the weak-shock or buzzer condition." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Integrating gay, lesbian, and bisexual issues into mainstream psychology.

Despite the growing clinical and research literature dealing with gay, lesbian, and bisexual (GLB) issues, mainstream psychology has tended to ignore much of the work that has been done in this area. This article illustrates how clinical and research writings on GLB issues continue to remain invisible to mainstream psychology in such areas as life span development and aging, teenage suicide, substance abuse, victimization and abuse, and family and couple relationships. It also deals with some of the determinants of well-being among GLB individuals, such as family support, and notes the benefits accruing to mainstream psychology from studying GLB issues. A network of family members within psychology having GLB relatives has been formed--AFFIRM: Psychologists Affirming their Gay, Lesbian, and Bisexual Family--and is dedicated to supporting its own family members, encouraging other family members to do likewise, supporting research and clinical work on GLB issues, and closing the gap between GLB clinical and research work and mainstream psychology. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Methods for the measurement of benzodiazepines in biological samples

A review of methods for the measurement of benzodiazepines in biological specimens published over the last five years is presented. A range of immunoassay procedures using EIA, ELISA, FPIA, agglutination or kinetic interaction of microparticles, or RIA methods are now available. Cross reactivities to benzodiazepines are variable such that no one kit will recognise all benzodiazepines and their relevant metabolites at concentrations likely to be encountered during therapeutic use. Prior hydrolysis of urine to convert glucuronide metabolites to immunoreactive substances improves detection limits for many benzodiazepines. Several radioreceptor assays have now been published and show good sensitivity and specificity to benzodiazepines and offer the advantage (over immunoassay) of being able to detect these drugs with equal sensitivity. Solvent extraction techniques using a variety of solvents were still popular and offer acceptable recoveries and lack of significant interference from other substances. A number of papers describing solid phase extraction procedures were also published. Direct injection of specimens into a HPLC column with back flushing were also successfully described. Seventy two chromatographic methods using HPLC, LC-MS, GC and GC-MS methods were reviewed. HPLC was able to achieve detection limits for many benzodiazepines using UV or DAD detection down to 1-2 ng/ml using 1-2 ml of urine or serum (blood). ECD detectors gave detection limits better than 1 ng/ml from 1 ml of specimen, which was an order of magnitude lower than for NPD. EI-MS offered similar sensitivity, whilst NCI-MS was capable of detection down to 0.1 ng/ml. Methods suitable for the separation of enantiomers of benzodiazepines have been described using HPLC. Electrokinetic micellar chromatography has also been shown to be capable of the analysis of benzodiazepines in urine.     

Cognitive–behavioral therapy helps prevent relapse and recurrence of panic disorder following alprazolam discontinuation: A long-term follow-up of the Peoria and Dartmouth studies.

The present research evaluated patients from 2 previous studies (1 conducted in Peoria, the other at Dartmouth) during a 2- to 5-year posttreatment period. Results showed that 75% of the Peoria sample and 76% of the Dartmouth sample were able to discontinue alprazolam therapy, remain abstinent of any type of treatment for panic disorder, and maintain their acute-treatment clinical gains over this follow-up period. The degree to which patients' anxiety sensitivity declined during treatment predicted relapse versus survival during the 1st 6 months of follow-up, when most relapses occurred. Implications of these findings for benzodiazepine discontinuation, combined pharmacotherapy and psychotherapy, and relapse prevention in panic disorder are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A multidimensional meta-analysis of treatments for depression, panic, and generalized anxiety disorder: An empirical examination of the status of empirically supported therapies.

The authors report a meta-analysis of high-quality studies published from 1990-1998 on the efficacy of manualized psychotherapies for depression, panic disorder, and generalized anxiety disorder (GAD) that bear on the clinical utility and external validity of empirically supported therapies. The results suggest that a substantial proportion of patients with panic improve and remain improved; that treatments for depression and GAD produce impressive short-term effects; that most patients in treatment for depression and GAD do not improve and remain improved at clinically meaningful follow-up intervals; and that screening procedures used in many studies raise questions about generalizability, particularly in light of a systematic relation across studies between exclusion rates and outcome. The data suggest the importance of reporting, in both clinical trials and meta-analyses, a range of outcome indices that provide a more comprehensive, multidimensional portrait of treatment effects and their generalizability. These include exclusion rates, percent improved, percent recovered, percent who remained improved or recovered at follow-up, percent seeking additional treatment at follow-up, and data on both completer and intent-to-treat samples. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nursing management of anxiety and panic

There are many aspects of everyday life that provoke anxiety. Visits to hospitals, emergency departments, or outpatient clinics are among the most anxiety producing. Anxiety exists on a continuum from normal, which alerts us that we need to pay attention to what is happening to us, to severely dysfunctional, as occurs with some of the anxiety disorders. Regardless of where patients fall on the continuum, nursing interventions can be very helpful. The etiology of anxiety disorders is multidimensional, including genetic vulnerability, neurophysiological dysregulations, stressful life events, and developmental antecedents. Because of the complex nature of anxiety, treatment is usually a combination of medications (benzodiazepines and antidepressants), education (particularly self-management techniques), sensory interventions, psychotherapy, and cognitive-behavioral interventions. The nurse's role in assessment, intervention, and referral is critical.     

Panic attacks in the nonclinical population: An empirical approach to case identification.

Although self-reports of panic attacks are common among student populations, it is not clear that their panic experiences are actually comparable to those of patients with clinical anxiety disorders. An empirical approach was taken to this problem by using a cluster analysis procedure to identify Ss within 2 samples of university students who reported panic attack symptom profiles that resembled those of patients with panic disorder. Such empirically defined "clinical" panic attacks were reported by 7 and 8.1% of the 2 samples. This predominantly female group accounted for most of the increased psychopathology that has been reported in previous studies of nonclinical panic. (PsycINFO Database Record (c) 2010 APA, all rights reserved)