The presence of affective symptoms in panic disorder has often been reported. Data from The Cross-National Collaborative Panic Study (second phase) were analysed to address the role of dysthymia in panic disorder with respect to previous illness, current psychopathology and the outcome during an 8-week study of alprazolam and imipramine. A group of dysthymic patients without current or past major depressive episode was studied. The prevalences of dysthymia varied markedly across participating sites: 2–13%. Only a few clinical characteristics of dysthymic panic disorder patients were found. They had suffered from panic disorder for a few years more than patients without affective disorder and they were slightly older. The outcome after the 8-week drug trial was not significantly different from that of patients without affective disorder. Hence, dysthymia was not suggested to be of major clinical relevance for the phenomenology of panic disorder or for the outcome of drug treatment.

We report the case of a patient with major depression and obsessive-compulsive disorder who had simultaneously high serum citalopram, clomipramine, and alprazolam concentrations probably due to the reciprocal competitive inhibition of the cytochrome P450-catalyzed oxidative metabolism.

Alprazolam (a benzodiazepine in the group of the triazolo-benzodiazepines) is a potent drug for the treatment of panic disorder. This is possible due to four different interactions with neurotransmitter systems. First, it facilitates, as all diazepines, the inhibitory acitivity of gamma-amino-butyricacid (GABA). The chemical structure differs from the benzodiazepines by incorporation of the triazoloring. Due to this triazoloring, the drug has three additional modes of action. These modes of action inhibit the locus coeruleus which plays a role in the origin of panic disorder. A first specific action is a stimulation of the serotonergic system. Triazolobenzodiazepines are also α2-adrenoreceptor agonists. Both mechanisms are responsible for inhibition of the locus coeruleus. Triazolo-benzodiazepines inhibit the platelet-activating-factor (PAF). PAF stimulates the corticotropin-releasing-hormone (CRH). This hormone stimulates the locus coeruleus. CRH in patients with panic attacks is elevated. This could be a result of hyperactive metabolism of the right parahippocampal area, which is observed in patients with panic attacks. Triazolo-benzodiazepines decrease the activity of the locus coeruleus because of a low CRH-level due to inhibited PAF.

Objective -To examine the safety and efficacy of alprazolam as an outpatient detoxification agent. Mehtod - Two-year, prospective, uncontrolled study of detoxification from alcohol employing alprazolam in a North Wicklow day centre. The HAD scale was used to measure emotional change. Results -Detoxification was completed in 26 cases. Adverse effects were mild or absent. Significant changes were recorded in both HAD scale scores. Client and staff satisfaction ratings were both high. Conclusions - Alprazolam is a safe and effective detoxification agent in outpatients. The HAD scale provided an objective measure of changes in anxiety and depression in this group of alcoholics. The treated population were older and more often employed than were alcoholics treated in the parent psychiatric hospital.

The literature on alprazolam is reviewed. It is concluded that it is an effective anxiolytic but that it is not an antidepressant. When used in sufficiently high dosage it can block panic attacks, but it is not the only antipanic agent available. It may be used as an alternative to other benzodiazepines in the acute detoxification of alcoholics. It should be avoided where there is strong individual likelihood of abuse. Chronic usage (more than a few weeks) demands a very slow tapering of dosage. Carbamazepine may ameliorate withdrawal symptoms. The use of alprazolam in other conditions remains unproven.

L’alprazolam et le clobazam ont été comparés au cours d’une étude prospective randomisée en double aveugle d’une durée de quatre semaines, en stricte monothérapie à posologie ajustée en fonction de l’efficacité et de la tolérance du malade, chez 117 patients ambulatoires présentant un trouble névrotique anxieux selon les critères du DSM II, dont l’intensité était comprise entre 18 et 35 à l’échelle d’anxiété de Hamilton.

L’efficacité de l’alprazolam est significativement supérieure à celle du clobazam sur l’appréciation globale de l’efficacité selon le médecin (p = 0.04) et le malade (p = 0.03) sur l’un des symptômes-cibles (p = 0.02), sur la tolérance globale (p = 0.02), ainsi que sur le nombre d’effets secondaires (p = 0.05); il n’existe pas de différence significative entre les deux produits sur l’échelle de Hamilton ou sur la version abrégée à 24 items de l’échelle d’auto-évaluation B.A.T.E. (Bonis Anxiété Trait Etat). Les posologies journalières moyennes utilisées en fin d’essai ont été de 2.95 mg et 28.5 mg pour l’alprazolam et le clobazam respectivement.

Les résultats observés concernant l’efficacité et la tolérance des deux produits sont discutés en termes de comparabilité des groupes, de sous-catégories d’anxiété étudiées, de posologies utilisées, ainsi que des nuances observées selon qu’on raisonne en termes d’évaluation globale ou en termes d’échelles psychométriques.

The delineation of the symptoms of schizophrenia into positive and negative types has been an important trend in psychiatric research over the past decade. This approach reflects renewed interests in clinical description and in developing etiologic hypotheses. The responsivity of positive and negative symptoms to neuroleptic and other pharmacotherapies, an issue of considerable clinical and research importance, however, remain in controversy.

We have observed that double-blind fluphenazine administration to 19 schizophrenic inpatients who had been maintained free from neuroleptic treatment for an extended period of time resulted in significant decreases in both positive as well as negative symptoms. The time course of symptom change differed, however, and the change in symptoms was not correlated, suggesting that the underlying pathophysiologies of positive and negative symptoms are only partially overlapping. The relative balance between positive and negative symptoms in individual patients, a putative schizophrenia trait characteristic, was found to be significantly altered by neuroleptic treatment, raising questions about the reliability of this classification approach.

In longitudinal studies in which plasma levels of the dopamine metabolite, homovanillic acid (HVA), were measured, change in negative symptoms associated with neuroleptic withdrawal and treatment were correlated, respectively, with changes in levels of plasma HVA. These data further support a relationship between negative symptoms and dopaminergic function. In addition to neuroleptic-induced reductions in negative symptoms, the augmentation of neuroleptic antipsychotic effects by the triazolobenzodiazepine, alprazolam, includes improvement in negative and positive symptoms in responsive patients.

These data including longitudinal studies of individual patients suggest that negative as well as positive symptoms respond to pharmacologic intervention. The clinical and research implications of these findings are discussed.