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Background: Benzodiazepines are treatment mainstays for several disorders, but there is often concern about dependency and addiction. In January 1989, New York implemented regulations requiring physicians to order benzodiazepines using state-monitored triplicate prescription forms. Objective: The purpose of this study was to assess the effects of the triplicate prescription program (TPP) on changes in use of benzodiazepines and other psychoactive drugs in clinically vulnerable Medicaid populations. Methods: Using an interrupted time series with comparison series design, psychoactive medication use was examined in the New York (intervention) and New Jersey (control) Medicaid programs before and after implementation of the New York benzodiazepine TPP among community-dwelling Medicaid beneficiaries aged ≥19 years continuously enrolled from January 1988 through December 1990 in New York or New Jersey with diagnoses of schizophrenia, schizophreniform disorder, schizoaffective disorder, schizoid personality disorder, or schizotypal personality disorder; bipolar disorder; epilepsy; and/or panic disorder, agoraphobia without history of panic disorder, social phobia, or specific phobia. Results: A total of 125,837 New York and 139,405 New Jersey Medicaid beneficiaries were continuously enrolled and met the study inclusion criteria. Of these, there were 6054 Medicaid enrollees in New York and 6875 enrollees in New Jersey who were clinically vulnerable patients with ≥1 of the specified diagnoses. New York Medicaid patients with any of these diagnoses experienced a −48.1% relative change (95% CI, −50.0% to −46.2%) in benzodiazepine use at 6 months after TPP implementation, with no decline in use in New Jersey patients. The largest reduction in benzodiazepine use was seen among patients with seizure disorder (−59.9% at 6 months; 95% CI, −63.9% to −55.9%). Although use of substitute drugs increased slightly in New York after the TPP, it did not offset reductions in benzodiazepine use. The effects of TPP were sustained for 7 years of follow-up and had the greatest impact on nonproblematic benzodiazepine use. Conclusions: During the time period studied in this analysis, the New York TPP reduced benzodiazepine use among chronically ill patients for whom these agents represent effective treatment. Our findings suggest that many patients previously receiving benzodiazepines did not receive any pharmacologic intervention.

Recently, pharmacological treatment guidelines for panic disorder have changed as newer treatment options have become available. The authors examined how the use of psychotropic drugs has shifted over the course of 10 years to determine if prescribing patterns have changed to reflect these revised treatment guidelines.A total of 443 patients with panic disorder were enrolled in the Harvard/Brown Anxiety Research Project, a prospective longitudinal study of anxiety disorders. These patients were interviewed over the course of 10 years to examine their use of psychotropic medications.Despite efforts aimed at increasing the use of selective serotonin reuptake inhibitors (SSRIs) in patients with panic disorder (e.g., APA's practice guideline for panic disorder, Food and Drug Administration approval of particular SSRIs for the treatment of panic disorder), only a modest increase in their use was found. Treatment patterns for psychotropic drugs appear to have remained stable over the past decade, with benzodiazepines being the most commonly used medication for panic disorder. In comparison, SSRI use throughout the follow-up period has remained low. Patients using an SSRI did not have a more favorable clinical course than those using a benzodiazepine, nor were there significantly better rates of remission in patients using SSRIs and benzodiazepines concomitantly.These results highlight a gap between pharmacological treatment guidelines and actual delivery of care in that recommendations to use SSRIs to treat panic disorder are not being followed. Factors potentially associated with promoting and ignoring treatment recommendations are discussed.

Objectives To review progress made during the past decade in late-life mood disorders and to identify areas of unmet need in health care delivery and research. Participants The Consensus Development Panel consisted of experts in late-life mood disorders, geriatrics, primary care, mental health and aging policy research, and advocacy. Evidence (1) Literature reviews addressing risk factors, prevention, diagnosis, treatment, and delivery of services and (2) opinions and experiences of primary care and mental health care providers, policy analysts, and advocates. Consensus Process The Consensus Development Panel listened to presentations and participated in discussions. Workgroups considered the evidence and prepared preliminary statements. Workgroup leaders presented drafts for discussion by the Consensus Development Panel. The final document was reviewed and edited to incorporate input from the entire Consensus Development Panel. Conclusions Despite the availability of safe and efficacious treatments, mood disorders remain a significant health care issue for the elderly and are associated with disability, functional decline, diminished quality of life, mortality from comorbid medical conditions or suicide, demands on caregivers, and increased service utilization. Discriminatory coverage and reimbursement policies for mental health care are a challenge for the elderly, especially those with modest incomes, and for clinicians. Minorities are particularly underserved. Access to mental health care services for most elderly individuals is inadequate, and coordination of services is lacking. There is an immediate need for collaboration among patients, families, researchers, clinicians, governmental agencies, and third-party payers to improve diagnosis, treatment, and delivery of services for elderly persons with mood disorders.

Antipsychotics, whether conventional or atypical, are the primary class of medications for the treatment of late-life psychosis. Although the efficacy of neuroleptics in controlling agitation and psychosis associated with late-life dementia has been established, evidence for their efficacy in treating core symptoms of late-life schizophrenia other than behavioral dyscontrol is just emerging. More controlled clinical trials are needed. The available data suggest that atypical neuroleptics are therapeutically efficacious, with a more favorable side-effect profile than conventional neuroleptics. This literature further suggests the importance of low therapeutic doses and careful attention to the emergence of side effects. Future studies must distinguish between patients with true schizophrenic disorder and patients with psychosis secondary to dementia, affective illness, or organic impairment. Patients must be characterized further as having EOS versus LOS because these disorders may differ in symptom profile, course, and response to treatment. There is also a need in future studies to separate out the results of treatment of patients with EOS who have been severely ill for most of their lives from those whose course has been less devastating. Within these two groups, treatment response, effective dose ranges, and sensitivity to side effects can be scrutinized more carefully.

Background Acute and chronic administration of the selective serotonin reuptake inhibitors (SSRIs) have been widely reported to disrupt sleep in laboratory studies. This study examines the naturalistic, longitudinal effects of paroxetine and fluvoxamine on sleep quality in the home setting. Method Fourteen healthy volunteers free of medical and neuropsychiatric symptoms entered a 31-day protocol: 7 days of drug-free baseline (days 1-7), 19 days of drug treatment (steady state during days 18-26), and 5 days of acute withdrawal (days 27-31). On day 8, the subjects were randomly assigned to receive either 100 mg/day of fluvoxamine or 20 mg/day of paroxetine (half receiving each drug) in divided morning and evening oral doses. Investigators remained blinded to drug assignment until all sleep data had been analyzed. Sleep was monitored using the Nightcap ambulatory sleep monitor. Four standard and 3 novel measures were computed and compared using multivariate analysis of variance, analysis of variance, and Bonferroni-corrected comparison of means. Results Sleep disruption was most clearly demonstrated using the novel measures eyelid quiescence index, rhythmicity, and eyelid movements per minute in non-rapid eye movement sleep, but was also apparent as determined by standard measures of sleep efficiency, number of awakenings, and sleep onset latency. Paroxetine disrupted sleep more than fluvoxamine, and paroxetine-induced sleep disruption persisted into the withdrawal phase. Rapid eye movement sleep was suppressed during treatment (especially for fluvoxamine) and rebounded during withdrawal (especially for paroxetine). Conclusion We confirm laboratory polysomnographic findings of SSRI-induced sleep quality changes and demonstrate the Nightcap's efficacy as an inexpensive longitudinal monitor for objective sleep changes induced by psychotropic medication.

SummaryIn older as well as younger people, antipsychotic medication is commonly used to treat psychoses. In clinical practice, antipsychotic medication is also used to control severe behavioral disturbances such as agitation, wandering, self-mutilation, as well as assaultiveness. Neuroleptic and non-neuroleptic drug treatments are used to control severe agitation and disruptive behavior.Among typical neuroleptics, very low doses (e.g., 0.25 mg of haloperidol 1–4 times per day) may be effective and limit the development of severe extrapyramidal reactions.Recent experience suggests that the atypical neuroleptics, olanzaine, risperidone, and quetiapine, are also useful for controlling severe agitation in elderly demented nursing home residents.The benzamides are also known for the treatment of behavioral disturbances in Europe, but there is little experience in the U.S.A.Although research studies in this area are virtually nonexistent, growing clinical experience sugests that the following may be quite useful: 1) trazodone; 2) buspirone (Buspar®); 3) anticonvulsants (e.g., valproate); and 4) β-blockers.

Clinical lore and a small number of published studies report that the selective serotonin reuptake inhibitors (SSRIs) intensify dreaming. This study examines the dream effects of paroxetine and fluvoxamine in order to both increase clinical knowledge of these agents and to test an important potential method for probing the relationship between REM sleep neurobiology and dreaming in humans. Fourteen normal, paid volunteers (4 males, 10 females; mean age 27.4 year, range 22--39) free of medical or neuropsychiatric symptoms as well as of psychotropic or sleep affecting drugs completed a 31-day home-based study consisting of: 7 days drug-free baseline; 19 days on either 100 mg fluvoxamine (7 Ss) or 20 mg paroxetine (7 Ss) in divided morning and evening doses; and 5 days acute discontinuation. Upon awakening, subjects wrote dream reports, self-scored specific emotions in their reports and rated seven general dream characteristics using 5-point Likert scales. Dream reports were independently scored for bizarreness, movement and number of visual nouns by three judges. REM sleep-related measures were obtained using the Nightcap ambulatory sleep monitor. Mean dream recall frequency decreased during treatment compared with baseline. Dream report length and judge-rated bizarreness were greater during acute discontinuation compared with both baseline and treatment and this effect was a result of the fluvoxamine-treated subjects. The subjective intensity of dreaming increased during both treatment and acute discontinuation compared with baseline. Propensity to enter REM sleep was decreased during treatment compared with baseline and acute discontinuation and the intensity of REM sleep increased during acute discontinuation compared with baseline and treatment. The decrease in dream frequency during SSRI treatment may reflect serotonergic REM suppression while the augmented report length and bizarreness during acute SSRI discontinuation may reflect cholinergic rebound from serotonergic suppression.

Clozapine is a new neuroleptic drug that was released for clinical use in the United States in February 1990 under the trade name Clozaril. Its availability is limited by an expensive mandatory sys...

Much progress has been made in understanding the nature, causes and treatment of late-life depressive disorders. Early diagnosis and treatment of depression in the elderly remains challenging to the clinician, but ultimately provides opportunities to reduce suffering and increase quality of life, to prevent suicide, to restore optimal levels of function and independence and to decrease the societal costs of healthcare. Late-life depression must not be considered a natural part of the aging process. Despite the challenges and complications of diagnosing late-life depression, it is possible both to recognize the symptoms and initiate treatment. Anti-depressants have proved both safe and effective, and are beneficial in combination with psychotherapy. Additional elderly-specific studies are at present under way to determine more fully the nature of late-life depression, and to inform diagnostic and treatment strategies.

OBJECTIVE: Nurses commonly observe more depression than is diagnosed and treated in nursing homes. Accordingly, we aimed to describe the clinical features of untreated nursing home residents whom nurses identify as depressed and to compare nurse ratings of depressed nursing home residents with ratings from direct interviews and patient self-reports. DESIGN: Cross-sectional survey followed by semi-structured diagnostic interviews of depressed patients and their nurses. SETTING: A large academic, multi-level, long-term care facility. PARTICIPANTS: Thirty-seven patients aged 74–99 (mean age 88.4) whom nurses identified as having daily symptoms of depression. Subjects had Mini-Mental State Exam (MMSE) scores >10 (mean score 21.2), were not acutely or terminally ill, and were able to participate in an interview. MEASUREMENTS: DSM-III-R mood diagnoses and separate ratings of interviews with nurses and patients using the Cornell Scale for Depression. RESULTS: Nurses observed daily symptoms of depression in 110 of 495 (22%) long-term care residents on units not reserved for advanced dementia. Of these 110 patients, 58 (53%) were not receiving antidepressants. Of 37 patients eligible for interviews, nine met criteria for major depression, 20 met criteria for another non-major depression diagnosis, and eight did not have a diagnosable mood disorder. Cornell scale ratings derived exclusively from interviews of nurses were similar across the three diagnostic groups (12.5, 9.9, and 9.5, respectively; P = .31; mean 10.5), whereas Cornell scale ratings from patient interviews differed among groups (15.9, 6.9, and 4.1, respectively; P < .001; mean 8.4). Correlation between nurse Cornell ratings and patient Cornell ratings was poor (r = .27), especially for patients with non-major forms of depression (r = -.20). MMSE and Cumulative Illness Rating Scale (CIRS-G) scores were similar in the three groups. CONCLUSIONS: Nurses frequently observed symptoms of depression in a long-term care setting, and many symptomatic patients were not being treated with antidepressants. In these patients, nurse-derived symptom ratings did not vary across DSM-III-R diagnostic categories and correlated poorly with ratings from direct patient interviews. These findings suggest that nurse caregivers may contribute important diagnostic information about non-major depression and raise questions about the application of standard diagnostic categories to late-life depression in the nursing home.

(MAOIs) may be especially effective in the treatment of bipolar depression that is refractory to tricyclic antidepressants, especially depression with anergic features (7). There are no studies comparing the efficacy of MAOIs and selective serotonin reuptake inhibitors (SSRIs) in the treatment ofbipolar depression. Limited published studies have suggested that SSRIs appear to be as effective and possibly more effective than older agents in treating bipolar depression (6,8). Bupropion is also

Clinical data and uncontrolled observations have suggested that fluoxetine is helpful in some patients with borderline personality disorder. This article describes the results of a 13-week double-blind study of volunteer subjects with mild to moderately severe borderline personality disorder. Thirteen fluoxetine recipients and nine placebo recipients received treatment. Pretreatment and posttreatment measures were obtained for global mood and functioning, anger, and depression. The most striking finding from this study was a clinically and statistically significant decrease in anger among the fluoxetine recipients. This decrease was independent of changes in depression. These data support previous observations that fluoxetine may reduce anger in patients with borderline personality disorder. The number of subjects in this study was small, the placebo responsiveness was high, and the clinical characteristics of the patients were in the mild to moderate range of severity. The data cannot be extrapolated to more severely ill borderline patients, but further study of fluoxetine and other selective serotonin reuptake inhibitors is indicated in this population.

Risperidone appears to be a significant advance in the treatment of schizophrenia. Its effectiveness for other serious psychiatric conditions, such as schizoaffective disorder and manic-depressive illness, has not been systematically studied. Further research is also needed to examine whether risperidone will be beneficial and adequately tolerated in special patient populations, including adolescents, the elderly, and psychiatric patients with concomitant medical illnesses.

Current evidence suggests that anxiety has a neurobiologic basis. It is thought to be caused by dysfunction of one or more neurotransmitters and their receptors. Most data, which are derived from study of the benzodiazepine-gamma-aminobutyric acid receptor complex, indicate that alteration of the influx of chloride ions within this receptor complex is associated with the development of anxiety. The primary therapeutic effect of benzodiazepines occurs at this receptor complex. All clinically available benzodiazepines are active at this receptor complex, producing therapeutic results and side effects. Subtypes of benzodiazepine receptors as well as endogenous benzodiazepine ligands also have been identified. These may play a role in the pathogenesis of anxiety. Benzodiazepines also modulate the production of neuroactive steroids in the central nervous system. In the future, drugs that affect these varying benzodiazepine functions may play a role in the treatment of anxiety. Other neurotransmitters also have been implicated in the genesis of anxiety. Drugs affecting the noradrenergic beta receptor and the 5-hydroxytryptamine (serotonin) receptors have anxiolytic properties. New evidence also suggests a role for adenosine and cholecystokinin in the development of anxiety; drugs interacting with these neurotransmitters also may have anxiolytic properties.

We have previously shown that perceptual judgements of motion direction are based in part on the activity of direction selective neurons in extrastriate visual area MT (Salzman et al., 1990, 1992). In those experiments, we applied low-amplitude microstimulation pulses (10 microA, 200 Hz) to clusters of MT neurons whose preferred directions were similar. The effect of microstimulation was to bias the monkeys' choices on a direction discrimination task toward the preferred direction of neurons at the stimulation site. The results suggest that microstimulation generated a directionally specific cortical signal by activating selectively neurons near the electrode tip. To test this notion more directly, we have now examined the behavioral effects of varying current amplitude, current frequency, and electrode position. In the majority of experiments, the directional bias in the monkeys' choices was reduced or eliminated as current amplitude increased to 80 microA. In addition, 80 microA stimulating pulses frequently impaired overall performance as measured by the percentage of correct responses. This decrement in performance indicated that 80 microA pulses introduced “noise” into the neural circuitry encoding motion direction, presumably by increasing current spread to activate a larger population of neurons representing all directions of motion. In contrast, increasing current frequency to 500 Hz (10 microA pulses) preserved the directional specificity of microstimulation effects. The precise position of the stimulating electrode also influenced the magnitude of microstimulation effects; in some cases, differences in position on the order of 100 microns determined whether an experiment yielded a very large effect or no effect at all. Thus, directionally specific activation of cortical circuitry within MT can be disrupted by increases in current spread or by small changes in electrode position. These observations suggest that the effects of low-amplitude microstimulation depend upon direct activation of a well-localized population of neurons.

Physiological and behavioral evidence suggests that the activity of direction selective neurons in visual cortex underlies the perception of moving visual stimuli. We tested this hypothesis by measuring the effects of cortical microstimulation on perceptual judgements of motion direction. To accomplish this, rhesus monkeys were trained to discriminate the direction of motion in a near-threshold, stochastic motion display. For each experiment, we positioned a microelectrode in the middle of a cluster of neurons that shared a common preferred direction of motion. The psychophysical task was then adjusted so that the visual display was presented directly over the neurons' receptive field. The monkeys were required to discriminate between motion shown either in the direction preferred by the neurons or in the opposite direction. On half the trials of an experiment, we applied electrical microstimulation while monkeys viewed the motion display. We hypothesized that enhancing the neurons' discharge rate would introduce a directionally specific signal into the cortex and thereby influence the monkeys' choices on the discrimination task. We compared the monkeys' performance on “stimulated” and “nonstimulated” trials in 139 experiments; all trials within an experiment were presented in random order. Statistically significant effects of microstimulation were obtained in 89 experiments. In 86 of the 89 experiments with significant effects (97%), the monkeys indicated that motion was in the neurons' preferred direction more frequently on stimulated trials than on nonstimulated trials. The data demonstrate a functional link between the activity of direction selective neurons and perceptual judgements of motion direction.

The following conclusions may be drawn from this article: 1. The age at which subjects are considered "elderly" or "geriatric" varies from study to study. By convention, age 65 is usually taken as the minimum age, yet virtually all studies cited included subjects below 65. Indeed, in a majority of studies, most of the subjects were below the conventional age of 65. Defining the minimum age for geriatric psychopharmacology studies is particularly important because there may be considerable pharmacodynamic and pharmacokinetic heterogeneity in people aged 65 and older. Clinical experience suggests that patients below age 80 tend to respond to medications like late middle-age adults, whereas those above age 80, as a group, are more sensitive to drugs. Because people 80 and above constitute the fastest growing group of Americans, it is essential to conduct more therapeutic clinical trials using them as research subjects. Information gathered from persons aged 60 to 79 may not be relevant to this older age group. 2. The total number of individuals studied in carefully controlled, double-blind research studies of MAOIs, atypical antidepressants, or psychomotor stimulants are relatively few when compared with the number of individuals studied with tricyclic antidepressants, or the number of nonelderly subjects studied. 3. Although many older persons are included in mixed-age research populations, the number of studies specifically designed in the elderly is also remarkably few. 4. In those studies that did focus on older patients, the definition of elderly was extended "downward" to include patients at age 55, or even 50. Whether or not this was done in order to enhance research subject recruitment, the net result is to vitiate any overall conclusion regarding the efficacy of drugs in patients over age 65, the usual lower cutoff for "elderly" or "geriatric" definition. 5. With the exception of a handful of patients receiving fluoxetine and methylphenidate, virtually no research patient above the age of 80 has been studied using any of the compounds discussed in this article. 6. Some of the double-blind studies reviewed are more than a decade old and techniques in research design have changed substantially since those studies were conducted. Many of the earlier studies would not be acceptable according to contemporary research design criteria because of inappropriate or inadequate inclusion criteria, inappropriate or inadequate outcome criteria, and inappropriate or inaccurate diagnostic criteria.(ABSTRACT TRUNCATED AT 400 WORDS)

Publisher Summary To meet the needs of increasing numbers of older patients, the field of geriatric psychopharmacology has developed from a fledgling area of inquiry into a major subspecialty within the field of general psychopharmacology during the past dozen years. Both research and clinical experience have vastly increased the knowledge database on the specific use of psychotropic drugs for older people and on nondrug factors that influence the effects of psychotropic drugs in this population. Psychotropic drug treatment for geriatric patients requires an understanding of several age-related factors that influence the effects of these drugs. Diagnosis, variable treatment response, and increased predisposition to drug side-effects provide the essential foundation. This chapter presents four additional areas of information that bear directly and indirectly upon appropriate and successful psychotropic drug use for this population. They are: (1) high prevalence of concomitant physical illness; (2) increased likelihood of the use of multiple drugs and the consequent potential for harmful drug interactions; (3) increased sensitivity of the aging central nervous system to the effects of psychotropic drugs; and (4) alterations in the aging body's ability to bind, distribute, and dispose of psychotropic drugs. Some clinical emphases governing the clinician's rational use of psychotropic drugs become evident: (1) choosing drug treatment when all other treatment modes prove ineffective; (2) being familiar with age-related changes intrinsic to psychotropic side effects; (3) appreciating the great diversity of the elderly population; and (4) recognizing the cautions necessary for safe psychotropic drug use when it is needed.

It is not uncommon in everyday clinical practice to hear the suggestion of a causal link between the use of benzodiazepines and the emergence ofdepressive symptoms. However, the standard reference manuals are far from clear on this issue. One recent pharmacologic text states that “occasional patients become depressed during chronic benzodiazepine therapy, but whether there is a causal association remains in doubt” (1). Another does not mention depression in the list of potential side effects of benzodiazepines (2). However, the report ofthe American Psychiatric Association’s task force on benzodiazepine toxicity states that although depression is not a frequent side effect, “Benzodiazepines have been reported to cause or exacerbate symptoms ofdepression” (3). In a standard pharmacologic textbook, depression is noted to be an occasional side effect of benzodiazepine use (4). The purpose of this column is to review the relationship between benzodiazepines and depression.

The same week that Sandoz Pharmaceuticals began marketing clozapine under the brand name Clozaril, the National Association of State Mental Health Program Directors (NASMHPD) sponsored a meeting in Arlington, Virginia, to discuss concerns about the drug’s unusual distribution system, its high cost, and how states can fund treatment for patients unable to pay it. Sandoz has estimated that approximately 200,000 patients are suitable candidates forclozapine. At least 80 percent of these patients receive their care in the public sector. The meeting, held February 8 and 9, was organized and moderated by Herndon P. Harding, Jr., M.D., commissioner of mental health in Ohio. Those attending the first day included medical directors, deputy commissioners, and delegates from 22 states as well as representatives of the Department of Veterans Affairs. On the second day they were joined by Sandoz officials and representatives of the National Alliance for the Mentally Ill, the Food and Drug Administration (FDA), the General Accounting Office (GAO), and various pharmacy professional organizations. Aides to Senator Edward M. Kennedy (D.-Mass.) also attended.

Clinicians have long recognized that disulfiram is a useful adjunct for the management of alcohol-abusing patients because the drug diminishes the risk of impulsive drinking in otherwise well-motivated patients. Careful monitoring and attention to drug interactions may extend this same benefit to schizophrenic patients who abuse alcohol.

Psychiatry has searched for a humane and effective treatment for the disruptive behavior and agitation that accompanies acute psychosis. Prior to the introduction of psychotropic drugs, baths, physical restraints, wet packs, and ECT [1] were used to manage agitated and assaultive conduct. Early pharmacological therapies included insulin coma, bromides, and barbiturates. Although useful for quieting some patients, these physical and pharmacologic approaches had serious complications and often lost effectiveness over time.