Psychotherapeutic Drugs Research Articles

精神科・一般病院グループ実習の試み

We previously reported the results of a questionnaire survey indicating that it would be feasible for training pharmacy students from general hospitals to take part in group practical training conducted in the pharmacy departments of psychotherapeutic hospitals. In the present study, we conducted a group hospital internship for pharmacy students from five psychotherapeutic hospitals and one general hospital. Having the practical training at psychotherapeutic hospitals significantly increased the students' knowledge of psychotherapeutic drugs and enabled any prejudice concerning psychiatric therapy to be quickly dispelled. However, since there were certain aspects of general pharmaceutical training that could not be covered by the psychotherapeutic hospitals, their pharmacists requested the pharmacists at the general hospital to conduct training in such aspects at a later date. Upon evaluating their pharmacy students, the pharmacists at the general hospital concluded that the group hospital internship had not reduced the knowledge or practical skills gained by the students. We would next like to develop a method for quantitatively evaluating such group internships.

Molecular mechanisms underlying emotional learning and memory in the lateral amygdala.

Fear conditioning is a valuable behavioral paradigm for studying the neural basis of emotional learning and memory. The lateral nucleus of the amygdala (LA) is a crucial site of neural changes that occur during fear conditioning. Pharmacological manipulations of the LA, strategically timed with respect to training and testing, have shed light on the molecular events that mediate the acquisition of fear associations and the formation and maintenance of long-term memories of those associations. Similar mechanisms have been found to underlie long-term potentiation (LTP) in LA, an artificial means of inducing synaptic plasticity and a physiological model of learning and memory. Thus, LTP-like changes in synaptic plasticity may underlie fear conditioning. Given that the neural circuit underlying fear conditioning has been implicated in emotional disorders in humans, the molecular mechanisms of fear conditioning are potential targets for psychotherapeutic drug development.

Hormone therapy after endometrial cancer.

Endometrial carcinoma is listed under the absolute contraindications to hormone therapy (HT). According to current opinion, HT after stage I or II is still considered an option, and continuous combined oestrogen/progestogen replacement therapy (CCEPT) would be recommended. However, up to now, only observational studies have been put forward. Although none of these studies have established an increased rate of recurrence or mortality, alternatives such as phytopreparations and tibolone, or particular psychotherapeutic drugs, such as venlafaxine, should be considered for the relief of climacteric complaints. Progestogen-only therapy (PT) particularly has been considered. However, the currently discussed possible progestogen effects regarding an increased risk of breast cancer have to be taken into account. Indeed, the wider discussion about the gestagen effects regarding the risk of breast cancer is to be considered. Generally, after hysterectomy, at least for patients with cardiovascular risk factors, the preference today is to use low-dose oestrogen therapy (patches or gels) instead of CCEPT, and this is also now recommended for patients after endometrial cancer. This is to be noted because of the risk factors for endometrial carcinoma, such as hypertension, obesity, polycystic ovary syndrome (PCO) and diabetes mellitus. However, each form of HT should be only exceptionally recommended, and the patients must be informed about the risks that exist and the use of alternatives.

Medications and Breast-Feeding: A Guide for Pharmacists, Pharmacy Technicians, and other Healthcare Professionals Part III

Objective: To provide a guide for practicing pharmacists, pharmacy technicians, and other healthcare professionals so that they are able to counsel and advise breast-feeding mothers and fellow healthcare professionals on the safety and use of antiinfectives, vaccines, antiepileptics, benzodiazepines, psychotherapeutic drugs, and radiopharmaceuticals during breast-feeding. Data Sources: Primary texts used by the breast-feeding community ( Medications and Mothers' Milk, Drugs in Pregnancy and Lactation, Drugs and Human Lactation) were searched, as well as Micromedex, MEDLINE, PubMed, EMBASE, and EMBASE2 (1984–February 2004). Study Selection/Data Extraction: Multiple sources were used wherever available to validate the data, and primary articles were used to verify all tertiary source information. Search terms included breast-feeding, lactation, nursing, and medications, as well as specific drug names. Data Synthesis: Concerns regarding medication use during breast-feeding have caused mothers to either discontinue nursing or not take necessary medications. Complete avoidance of medications or cessation of breast-feeding is often unnecessary. Although there are drugs that can be harmful to nursing infants, breast-milk concentrations of most drugs are insufficient to cause any harm. Conclusions: Having objective and reliable information on medications enables pharmacists, pharmacy technicians, other healthcare providers, and mothers to make educated decisions regarding drug therapy and breast-feeding.

Structural effects and neurofunctional sequelae of developmental exposure to psychotherapeutic drugs: experimental and clinical aspects.

The advent of psychotherapeutic drugs has enabled management of mental illness and other neurological problems such as epilepsy in the general population, without requiring hospitalization. The success of these drugs in controlling symptoms has led to their widespread use in the vulnerable population of pregnant women as well, where the potential embryotoxicity of the drugs has to be weighed against the potential problems of the maternal neurological state. This review focuses on the developmental toxicity and neurotoxicity of five broad categories of widely available psychotherapeutic drugs: the neuroleptics, the antiepileptics, the antidepressants, the anxiolytics and mood stabilizers, and a newly emerging class of nonprescription drugs, the herbal remedies. A brief review of nervous system development during gestation and following parturition in mammals is provided, with a description of the development of neurochemical pathways that may be involved in the action of the psychotherapeutic agents. A thorough discussion of animal research and human clinical studies is used to determine the risk associated with the use of each drug category. The potential risks to the fetus, as demonstrated in well described neurotoxicity studies in animals, are contrasted with the often negative findings in the still limited human studies. The potential risk fo the human fetus in the continued use of these chemicals without more adequate research is also addressed. The direction of future research using psychotherapeutic drugs should more closely parallel the methodology developed in the animal laboratories, especially since these models have already been used extremely successfully in specific instances in the investigation of neurotoxic agents.

Psychopharmaco-hazardology: major hazards of treating depression and anxiety.

Balancing the benefits and risks of prescribing psychotherapeutic drugs requires knowledge of both drug hazards as well as risk of untreated psychiatric illness. Screening for medical illnesses, substance abuse, suicidality, and unusual side effects is essential throughout treatment.

Psychopharmacohazardology: major hazards of the new generation of psychotherapeutic drugs.

Balancing the benefits and risks of prescribing psychotherapeutic drugs requires knowledge of the baseline risks of genetics, lifestyle and morbidity of untreated illness. Superimposed upon these risks are some rare but potentially dangerous, uncomfortable or irreversible hazards of the antipsychotics, mood stabilizers, antidepressants and tranquillizers. Knowledge of these hazards facilitates monitoring and prompt intervention at the earliest sign of problems.

Factors associated with Ecstasy use in Turkish students.

The purpose of this study was to establish the factors associated with Ecstasy use in secondary school students in Turkey. This is a survey of a representative sample drawn from cities in different geographical regions in Turkey in 1998 and 2001. The questionnaire was administered to a total of 18,556 and 11,911 10th-grade students in 1998 and 2001, respectively. The questionnaire administered in the study was adapted from the questionnaires used in 'Monitoring the Future' study in the United States and ESPAD (the European School Survey Project on Alcohol and Other Drugs). It included questions about demographic characteristics, family characteristics, school life, social contacts and use of substances. While the percentage of those who used Ecstasy at least once in their life-times was 2.65% in 1998, the figure reached 3.31% in 2001. Male gender, older age, use of alcohol, cannabis, heroin and cocaine, non-medical use of psychotherapeutic drugs and participation in a meeting concerning the adverse effects of substance use were found to be significant variables predicting 'ever use' of Ecstasy in both years by logistic regression analysis. Ecstasy use, while low in Turkey, appears to be on the increase and follows a pattern in terms of correlates that is similar to other illicit drugs. Whatever the causes behind the rise in Ecstasy use, creative, personalized and informative educational programmes should be conducted in all educational institutions to curb Ecstasy use.

Role of hydrophobicity on the monoamine receptor binding affinities of central nervous system drugs: a quantitative retention–activity relationships analysis using biopartitioning micellar chromatography

Biological action and activity reflect an aspect of the fundamental physicochemical properties of the bioactive compounds. As an alternative to classical QSAR studies, in this work different quantitative retention–activity relationships (QRAR) models are proposed, which are able to describe the role of hydrophobicity on the binding affinity to different brain monoamine receptors (H 1-histamine, α 1-noradrenergic and 5-HT 2-serotonergic) of different families of psychotherapeutic drugs. The retention of compounds is measured in a biopartitioning micellar chromatography (BMC) system using Brij-35 mobile phases. The adequacy of the QRAR models developed is due to the fact that both the retention of compounds in BMC and the drug–receptor interaction are described by the same hydrophobic, electronic and steric properties of compounds. The obtained results indicate that, for structurally related compounds that present the same molecular features as the basic pharmacophore, there is a retention range in which compounds present the highest affinity to all of monoamine receptors.

Oxcarbazepine, topiramate, zonisamide, and levetiracetam: Potential use in neuropathic pain

Background: Oxcarbazepine, topiramate, zonisamide, and levetiracetam are the antiepileptic drugs (AEDs) most recently approved by the US Food and Drug Administration. Based on the experience with carbamazepine, gabapentin, and lamotrigine, these newer AEDs are being investigated for the management of neuropathic pain. Objective: This article reviews preclinical and clinical data on the efficacy and tolerability of these 4 AEDs in the management of neuropathic pain, as well as the pharmacokinetics, drug-interaction potential, adverse effects, and dosing of these agents, with an emphasis on their use in older individuals. Methods: Relevant studies were identified through a MEDLINE search of the Englidh-language literature published between 1986 and May 2003, a review of the reference lists of identified articles, and abstracts from the annual meetings of the American Academy of Neurology (1986–2002) and the 2003 Annual Meeting of the American Pain Society. Search terms were oxcarbazepine, topiramate, zonisamide, and levetiracetam. Results: Oxcarbazepine and topiramate have been effective in animal models of neuropathic pain. Thirty-four publications on the efficacy and tolerability of the 4 agents were identified (25 case reports/case series, 6 randomized parallel-group studies, and 3 randomized crossover studies). The 9 randomized studies were restricted to oxcarbazepine and topiramate, and 23 (68%) publications were available in abstract form only. These preliminary data suggest that the 4 newer AEDs may be useful in a wide variety of neuropathic pain syndromes; however, additional data, including full-length peer-reviewed reports, are necessary before their true analgesic potential in neuropathic pain can be determined. All 4 agents have pharmacodynamic interactions with other psychotherapeutic drugs, potentiating adverse central nervous system events such as sedation. With the exception of levetiracetam, these drugs also have pharmacokinetic interactions with other drugs, although to a somewhat lesser extent than carbamazepine. These agents have some unique adverse effects not frequently monitored by clinicians, such as hyponatremia, nephrolithiasis, acute myopia with secondary angle-closure glaucoma, and weight loss. Conclusions: Based on preliminary data, oxcarbazepine, topiramate, zonisamide, and levetiracetam may be useful in the treatment of a wide variety of neuropathic pain syndromes, although full publication of the results of controlled trials is awaited. These agents are associated with specific adverse effects not commonly monitored by clinicians. Of the 4, levetiracetam appears to be easiest to use (ie, no need for dose adjustment in organ dysfunction, no need for laboratory monitoring) and best tolerated, and has not been associated with the unique toxicities seen with oxcarbazepine, topiramate, and zonisamide. The ultimate role of these agents in the therapeutic armamentarium against pain requires further research and experience. In the interim, these 4 agents should be used to treat neuropathic pain in the elderly only when carbamazepine, gabapentin, or lamotrigine cannot be used or when the response to the aforementioned agents is suboptimal.

Monitoring the Future: National Results on Adolescent Drug Use: Overview of Key Findings

Monitoring the Future: National Results on Adolescent Drug Use: Overview of Key Findings

Review of the use of topiramate for treatment of bipolar disorders.

Lithium alone or in combination with other psychotherapeutic drugs has long been the gold standard of management for bipolar disorder (BD). Recognition of its limitations in the acute and chronic management of BD has led to the development of alternative therapies. One such approach involves the use of antiepileptic drugs (AEDs). The AED topiramate is currently being studied in the efficacy and management of BD. Topiramate has mechanisms in common with other AEDs, including sodium channel-blocking activity and enhancement of cerebral GABA concentrations. Open-label trials have evaluated topiramate at mean daily doses of 100 to 300 mg in various BD subtypes, including acute mania, depression, rapid-cycling, mixed states, and BD refractory to other medications. Results from these trials suggest topiramate may be efficacious in BD subtypes, particularly in rapid-cycling patients and those refractory to conventional treatment. Its side effect profile appears benign when used as monotherapy or in combination with other mood stabilizers. Placebo-controlled, double-blind studies are warranted to evaluate topiramate further in BD.

Cell pathology in mood disorders.

In new, exciting, neuroanatomic studies on postmortem tissues from patients with mood disorders, quantitative cytomorphologic differences can be shown at the microscopic level. These investigations provide direct evidence that mood disorders are characterized by marked reductions in glial cell number and density in addition to subtle alterations in the density and size of cortical neurons in frontolimbic brain regions. Importantly, this corresponds with clinical neuroimaging studies and preclinical animal studies that suggest cell atrophy, cell loss, or impairments in neuroplasticity and cellular resilience may underlie the neurobiology of major depressive disorder and bipolar manic-depressive disorder. Because this represents a departure from modern efforts to understand mood disorders, published reports are scarce and based on rather small sample sizes. This article reviews the current findings from postmortem studies on glial and neuronal cell counts in primary mood disorders and discusses a possible link between cellular changes and the action of psychotherapeutic drugs.

Evaluation of the Psychological Status in Chronic Low Back Pain: Comparison with General Population

Multiple studies have documented a strong association between chronic low back pain and psychopathology including personality disorders, depressive disorders, anxiety, and somatoform disorders along with non-specific issues such as emotion, anger and drug dependency. However, depression, anxiety and somatization appear to be crucial. There are no controlled trials in interventional pain management settings. This study was designed to evaluate 40 individuals without pain or psychotherapeutic drug therapy, Group I, control group; and Group II, chronic low back pain group with 40 chronic low back pain patients. All the participants were tested utilizing Pain Patient Profile (P3). Significant differences were found among various clinical syndromes with generalized anxiety disorder, somatoform disorder, and depression, with 0% vs 20%, 0% vs 20%, and 5% vs 30% in Group I and Group II consecutively. This evaluation showed that clinical syndromes were seen in a greater proportion of patients with chronic low back pain emphasizing the importance of evaluation of the patients for generalized anxiety disorder, somatoform disorder, and for depression.

Do Number of Pain Conditions Influence Emotional Status?

This study was designed to evaluate psychological status of 150 individuals; 50 without chronic pain and without psychotherapeutic drug therapy, Group I or control group; 50 patients with chronic pain, Group II, chronic pain group with involvement of one region; and 50 chronic pain patients with involvement of two or more regions, Group III. All the participants were tested utilizing Millon Clinical Multiaxial Inventory -III (MCMI-III). Results were analyzed and compared for various clinical personality patterns including personality traits and personality disorders; severe personality pathology for schizotypal, borderline and paranoid personality pathology; and multiple clinical syndromes including generalized anxiety disorder, somatization disorder, major depression, bipolar manic disorder and dysthymic disorder, etc. There were no significant differences noted in clinical personality patterns or severe personality pathology. In the analysis of clinical syndromes, generalized anxiety disorder, somatization disorder, and depressive disorders were seen in a progressively greater proportion of patients in Groups I to III. In conclusion, this evaluation showed that abnormal clinical personality patterns are present in both groups of patients. Psychological abnormalities with generalized anxiety disorder, somatization disorder, and depression are commonly seen in chronic pain patients.

Comparison of the Psychological Status of Chronic Pain Patients and the General Population

This study was designed to evaluate the psychological status of 50 individuals without chronic pain and without psychotherapeutic drug therapy, Group I, the control group; and Group II, a chronic pain group with 100 chronic pain patients. All the participants were tested utilizing Millon Clinical Multiaxial Inventory III (MCMI-III). Results were analyzed and compared for various clinical personality patterns, including personality traits and personality disorders; severe personality pathology for schizotypal, borderline and paranoid personality pathology; and multiple clinical syndromes, including generalized anxiety disorder, somatization disorder, major depression, bipolar manic disorder and dysthymic disorder, etc. There were no significant differences noted in clinical personality patterns or severe personality pathology. In the analysis of clinical syndromes, generalized anxiety disorder (40% vs 14%), somatization disorder (26% vs 0%), and major depression (22% vs 4%) were seen in a greater proportion of patients in the chronic pain group. The prevalence of psychological disorders in the control group was 24%, compared to 55% in chronic pain group. In conclusion, this evaluation showed that clinical personality patterns are present in both groups of patients. Psychological abnormalities such as generalized anxiety disorder, somatization disorder, and major depression are commonly seen in chronic pain patients.

Psychological Effects of Exercise<br />with General and Diseased Populations

The general purpose of the current paper was to review the literature that has examined the psychological effects of exercise for both general and diseased populations. In the first three sections, a review of the effects of exercise on depression, pain, and anxiety were discussed. In the fourth section, exercise dependence, a negative psychological consequence of exercise, was defined and examined. In the fifth section, the interaction of exercise, with psychotherapeutic drugs was addressed. And finally, in the sixth section, implications for exercise prescription by clinicians were provided.

Electrophysiological characterization of laminar synaptic inputs to the olfactory tubercle of the rat studied in vitro: modulation of glutamatergic transmission by cholinergic agents is pathway-specific.

We have exploited the complementary arrangement of afferents in a coronal slice (300-400 microm) of the rat olfactory tubercle (OT) maintained in vitro to investigate transmission in two separate synaptic pathways. We recorded extracellular responses within the OT dense cell layer in slices and stimulated either the outermost layer to activate primary olfactory fibres or deeper to activate secondary input. Superficial stimulation produced a synaptic potential with superimposed population spike. This interpretation was based on blockade by calcium removal from the bathing medium and the use of the glutamate antagonist DNQX (10 microM); the spike was found to be selectively suppressed by tetrodotoxin applied near the cells. The spike, but not the synaptic wave, was depressed by 12 mM Ca2+ and enhanced by 1 mM Ba2+ in the bathing medium. Deep stimulation to activate association and intrinsic fibres elicited a nerve volley followed by a later response, also blocked by Ca2+ removal or 10 microM DNQX. It was unaffected by high Ca2+ or Ba2+, hence resulting from synaptic and not action current flow. Removal of Mg2+ from the bathing medium revealed an NMDA component of synaptic transmission at both loci that was selectively blocked by D-AP-5. The deep synaptic response, only, was depressed by carbachol IC50 7 microM or muscarine IC50 13 microM. This depression was also induced by AChE inhibitors eserine or tacrine and was antagonized by 1 microM atropine or 5-10 microM clozapine. These results characterize transmission in the OT and demonstrate a role for muscarinic modulation of deeper synapses in the OT that is influenced by psychotherapeutic drugs.

Psychotherapy and the single synapse: the impact of psychiatric thought on neurobiological research. 1979.

THE title of this lecture is at best premature and more likely absurd, but I have adopted it for two reasons. In the first place, I want to emphasize the continuing tension within psychiatry betwee...

An analysis of parotid salivary gland function with desipramine and age in female NIA Fischer 344 rats.

Cyclic antidepressants are still a dominating group of psychotherapeutic drugs used in the treatment of depression. Dry mouth is one of their major side effects. In this study we analyzed the effects of the long-term administration of the tricyclic antidepressant desipramine and the reversibility of this treatment following a 15-day washout period on different parameters in parotid gland function in aging rats. We hypothesized that glandular function would be decreased, and recovery delayed with age. Drug treatment affected body weight, glandular weight, DNA synthesis, and the concentration of soluble and structural membrane proteins. Surprisingly, parotid flow rate was increased with desipramine in all ages. While the concentration of secreted proteins was generally decreased with treatment, total proteins secreted were quite stable. SDS/PAGE analysis revealed prominent changes with desipramine. Amylase activity was depressed with treatment, but only low residual cellular enzyme activity was detected in the glandular supernatant. Therefore, a secretory impairment with desipramine was excluded. The content of the antimicrobial proteins peroxidase and lysozyme was increased with desipramine in all age groups. Most parameters measured revealed delayed recovery with age. These data indicate that the tricyclic antidepressant desipramine has profound effects on parotid gland function, accented with age.