The effect of selective serotonin reuptake inhibitor treatment of panic disorder on emergency room and laboratory resource utilization. The role of lysosomes in the cellular distribution of thioridazine and potential drug interactions. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Rx drugs

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J Clin Psychiatry. 2001 Sep;62(9):678-82.
The effect of selective serotonin reuptake inhibitor treatment of panic disorder on emergency room and laboratory resource utilization.

Roy-Byrne PP, Clary CM, Miceli RJ, Colucci SV, Xu Y, Grudzinski AN.

Department of Psychiatry and Behavioral Sciences, Universite of Washington School of Medicine, Seattle, USA.

BACKGROUND: While it has been well documented that patients with untreated panic disorder frequently utilize emergency room (ER) and laboratory services, no published data evaluate whether selective serotonin reuptake inhibitor (SSRI) treatment of patients with panic disorder is associated with decreased use of these services in the managed care organization setting. METHOD: A medical and pharmacy claims database representing individuals from several managed care organizations was used to analyze ER and laboratory resource utilization and cost for 120 patients with panic disorder (ICD-9-CM criteria) who received SSRI treatment. RESULTS: SSRI treatment was associated with a reduction in the mean number of ER and laboratory visits and costs in the 6-month period following therapy initiation compared with the 6-month period prior to therapy initiation (sertraline: visits, -79.5%; costs, -85.2%; p < .05; fluoxetine: visits, -25.0%; costs, -69.5%; p = NS; and paroxetine: visits, -8.6%; costs, -30.8%; p = NS). CONCLUSION: The results of the current study suggest that appropriate treatment of panic disorder may decrease unnecessary resource utilization for the medical symptoms associated with panic disorder.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11681762&dopt=Abstract

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Toxicol Appl Pharmacol. 1999 Jul 15;158(2):115-24.
The role of lysosomes in the cellular distribution of thioridazine and potential drug interactions.

Daniel WA, Wojcikowski J.

Polish Academy of Sciences, Institute of Pharmacology, Smetna 12, Krakow, 31-343, Poland.

The purpose of the present study was to investigate the contribution of lysosomal trapping to the total tissue uptake of thioridazine and to potential drug distribution interactions between thioridazine and tricyclic antidepressants (imipramine, amitriptyline) or selective serotonin reuptake inhibitors (SSRIs; fluoxetine, sertraline). The experiment was carried out on slices of various rat tissues as a system with intact lysosomes. Thioridazine and antidepressants (5 microM) were incubated separately or jointly with the tissue slices in the absence or presence of "lysosomal inhibitors," i.e., ammonium chloride or monensin. The results show that the contribution of lysosomal trapping to the total tissue uptake of thioridazine is as important as phospholipid binding. A high degree of dependence of thioridazine tissue uptake on the lysosomal trapping is the cause of substantial distributive interactions between thioridazine and the investigated antidepressants at the level of cellular distribution. Thioridazine and the antidepressants, both tricyclic and SSRIs, mutually decreased their tissue uptake. The potency of antidepressants to decrease thioridazine uptake was similar to that of lysosomal inhibitors. In general, the observed interactions between thioridazine and antidepressants occurred only in those tissues in which thioridazine showed lysosomotropism (the lungs, liver, kidneys, brain, and muscles) but were not observed in the presence of ammonium chloride. The above finding provides evidence that the interactions proceeded at the level of lysosomal trapping. In the adipose tissue and heart no lysosomal trapping of thioridazine was detected and those tissues were not the site of such an interaction. Since the organs and tissues involved in the distributive interactions constitute a major part of the organism and take up most of the total drug in the body, the interactions occurring in them may cause a substantial shift of the drugs to organs and tissues poor in lysosomes, e.g. the heart and muscles. An in vivo study into the thioridazine-imipramine interaction showed that joint administration of the drugs under study (10 mg/kg ip) increased drug concentration ratios of lysosome-poor tissue/plasma and lysosome-poor/lysosome-rich tissue. Considering serious side effects of thioridazine and tricyclic antidepressants (cardiotoxicity, anticholinergic activity), the thioridazine-antidepressant combinations studied should be approached with respect to the appropriate dose adjustment. Copyright 1999 Academic Press.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10406926&dopt=Abstract

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Biol Psychiatry. 2001 Nov 1;50(9):651-8.
Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study.

Sheline YI, Barch DM, Donnelly JM, Ollinger JM, Snyder AZ, Mintun MA.

Department of Psychiatry, Washington University, St. Louis, Missouri 63110, USA.

BACKGROUND: The amygdala has a central role in processing emotions, particularly fear. During functional magnetic resonance imaging (fMRI) amygdala activation has been demonstrated outside of conscious awareness using masked emotional faces. METHODS: We applied the masked faces paradigm to patients with major depression (n = 11) and matched control subjects (n = 11) during fMRI to compare amygdala activation in response to masked emotional faces before and after antidepressant treatment. Data were analyzed using left and right amygdala a priori regions of interest, in an analysis of variance block analysis and random effects model. RESULTS: Depressed patients had exaggerated left amygdala activation to all faces, greater for fearful faces. Right amygdala did not differ from control subjects. Following treatment, patients had bilateral reduced amygdala activation to masked fearful faces and bilateral reduced amygdala activation to all faces. Control subjects had no differences between the two scanning sessions. CONCLUSIONS: Depressed patients have left amygdala hyperarousal, even when processing stimuli outside conscious awareness. Increased amygdala activation normalizes with antidepressant treatment.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11704071&dopt=Abstract

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