Depression: Docherty JP

Alexopoulos GS, Katz IR, Reynolds CF, Carpenter D, Docherty JP, Anonymous00334. · No affiliation provided · Postgrad Med. · Pubmed #17205639 No free full text.

Abstract: OBJECTIVES: Depression in older patients contributes to personal suffering and family disruption and increases disability, medical morbidity, mortality, suicide risk, and healthcare utilization. The majority of clinical trials of antidepressant treatments are conducted in younger patients. For this reason, clinicians often have to extrapolate from studies in populations that do not present the same problems as older patients. For example, older patients often have serious coexisting medical conditions that may contribute to the depression and complicate the choice of treatment. Older patients as a rule need to be on many medications, some of which may contribute to depression and/or interact with antidepressants. Finally, older adults metabolize medications slowly and are more sensitive to side effects than younger patients. Because of these complexities, we conducted a consensus survey of expert opinion on the pharmacotherapy of depressive disorders in older patients to address clinical questions not definitively answered in the research literature. METHOD: After reviewing the literature and convening a work group of experts, we prepared a written survey with 64 questions that asked about 857 options. 618 of the options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For the other options, the experts were asked to write in answers (e.g., average doses) or to check a box to indicate their preferred answer. We sent the survey to 50 national experts on geriatric depression, all of whom completed it. Consensus on each option was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred choice, second line/alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on 89% of the options rated on the 9-point scale. The experts stress the importance of identifying coexisting medical conditions that may be contributing to the depression or complicate treatment. For unipolar nonpsychotic major depression, the preferred strategy is an antidepressant (selective serotonin reuptake inhibitor [SSRI] or venlafaxine XR preferred) plus psychotherapy. For unipolar psychotic major depression, the treatment of choice is an antidepressant (SSRI or venlafaxine XR) plus one of the newer atypical antipsychotics. Electroconvulsive therapy is also first line. For dysthymic disorder or persistent milder depression, the experts recommend combining an antidepressant (SSRIs preferred) and psychotherapy. If the patient has a comorbid medical condition (e.g., hypothyroidism) that is contributing to the depression, the experts recommend treating both the depression and the medical condition from the outset. The SSRIs were the top-rated antidepressants for all types of depression. Among them, the experts gave the highest ratings for efficacy and tolerability to citalopram and sertraline. Paroxetine was another first-line option, and fluoxetine was rated high second line. The preferred psychotherapy techniques for treating depression in older patients are cognitive-behavioral therapy, supportive psychotherapy, problem-solving psychotherapy, and interpersonal psychotherapy. The experts also give strong support to including appropriate psychosocial interventions (e.g., psychoeducation, family counseling, visiting nurse services) in the treatment program. The majority of experts would continue treatment with antidepressant medication for at least 1 year if a patient has had a single episode of severe unipolar major depression, for 1-3 years for a patient who has had 2 such episodes, and for longer than 3 years if there is a history of 3 or more episodes. CONCLUSIONS: The experts reached a high level of consensus on the appropriateness of including both antidepressant medication, specifically SSRIs, and nonpharmacological modalities in treatment plans for severe depression. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide direction for addressing common clinical dilemmas in older individuals. They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions. Nonetheless, the guidelines cannot address the complexities involved in the care of each individual patient and can be most helpful in the hands of experienced clinicians.

Kane JM, Leucht S, Carpenter D, Docherty JP, Anonymous00117. · No affiliation provided · J Clin Psychiatry. · Pubmed #14640142 No free full text.

Abstract: OBJECTIVES: A growing number of atypical antipsychotics are available for clinicians to choose from in the treatment of psychotic disorders. However, a number of important questions concerning medication selection, dosing and dose equivalence, and the management of inadequate response, compliance problems, and relapse have not been adequately addressed by clinical trials. To aid clinical decision-making, a consensus survey of expert opinion on the pharmacologic treatment of psychotic disorders was undertaken to address questions not definitively answered in the research literature. METHOD: Based on a literature review, a written survey was developed with 60 questions and 994 options. Approximately half of the options were scored using a modified version of the RAND 9-point scale for rating the appropriateness of medical decisions. For the other options, the experts were asked to write in answers (e.g., average doses) or check a box to indicate their preferred answer. The survey was sent to 50 national experts on the pharmacologic treatment of psychotic disorders, 47 (94%) of whom completed it. In analyzing the responses to items rated on the 9-point scale, consensus on each option was defined as a non random distribution of scores by chi-square "goodness-of-fit"test. We assigned a categorical rank (first line/preferred choice,second line/alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on 88% of the options rated on the 9-point scale. The experts overwhelmingly endorsed the atypical antipsychotics for the treatment of psychotic disorders. Risperidone was the top choice for first-episode and multi-episode patients, with the other newer atypicals rated first line or high second line depending on the clinical situation.Clozapine and a long-acting injectable atypical (when available)were other high second line options for multi-episode patients.The expert's dosing recommendations agreed closely with the package inserts for the drugs, and their estimates of dose equivalence among the antipsychotics followed a linear pattern.The experts considered 3-6 weeks an adequate antipsychotic trial, but would wait a little longer (4-10 weeks) before making a major change in treatment regimen if there is a partial response. The experts recommended trying to improve response by increasing the dose of atypical and depot antipsychotics before switching to a different agent; there was less agreement about increasing the dose of conventional antipsychotics before switching, probably because of concern about side effects at higher doses. If it is decided to switch because of inadequate response, risperidone was the expert's first choice to switch to, no matter what drug was initially tried. Although there was some disparity in the expert's recommendations concerning how many agents to try before switching to clozapine, the expert's responses suggest that switching to clozapine should be Clozapine was also the antipsychotic of choice for patients with suicidal behavior. When switching oral antipsychotics,the experts considered cross-titration the preferred strategy. When switching to an injectable antipsychotic, the experts stressed the importance of continuing the oral antipsychotic until therapeutic levels of the injectable agent are achieved.The experts considered psychosocial interventions the first choice strategy for partially compliant patients, with pharmacologic interventions the first choice for patients with clear evidence of noncompliance. However, because it can be difficult to distinguish partially compliant from noncompliant patients, the editors recommended combining psychosocial and pharmacologic interventions to improve compliance whenever possible.When patients relapse because of compliance problems or if there is any doubt about compliance, the experts recommended the use of a long-acting injectable antipsychotic and would select an injectable atypical when this option becomes available.The experts would also consider using an injectable atypical antipsychotic (when available) in many clinical situations that do not involve compliance problems.The experts stressed the importance of monitoring for health problems-especially obesity, diabetes, cardiovascular problems,HIV risk behaviors, medical complications of substance abuse, heavy smoking and its effects, hypertension, and amenorrhea-in patients being treated with antipsychotics.Although many patients are prescribed adjunctive treatments,multiple antipsychotics, and combinations of different classes of drugs (e.g., antipsychotics plus mood stabilizers or antidepressants) in an effort to enhance response, the experts gave little support to any of these strategies, with the exception of antidepressants for patients with dysphoria/depression, antidepressants or ECT for patients with suicidal behavior, and mood stabilizers for patients with aggression/violence.When asked about indicators of remission and recovery, the experts considered acute improvement in psychotic symptoms the most important indicator of remission, whereas they considered more sustained improvement in multiple outcome domains (e.g., occupational/educational functioning, peer relationships,independent living) important in assessing recovery. CONCLUSIONS: The experts reached a high level of consensus on many of the key treatment questions in the survey. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide direction for addressing common clinical dilemmas that arise in the pharmacologic treatment of psychotic disorders. They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions. Clinicians should keep in mind that no guidelines can address the complexities involved in the care of each individual patient and that sound clinical judgment based on clinical experience should be used in applying these recommendations.

Altshuler LL, Cohen LS, Moline ML, Kahn DA, Carpenter D, Docherty JP, Anonymous00291. · UCLA Neuropsychiatric Institute, VA Greater Los Angeles Healthcare System, USA. · Postgrad Med. · Pubmed #11500997 No free full text.

Abstract: OBJECTIVES: Women constitute two-thirds of patients suffering from common depressive disorders. The treatment of depression in women is therefore a substantial public health concern. High-quality, empirical data on depressive disorders specific to women are limited. As a result, there are no comprehensive evidence-based practice guidelines on the best treatment approaches for these illnesses. We conducted a consensus survey of expert opinion on the treatment of 4 depressive conditions specific to women: premenstrual dysphoric disorder (PMDD), depression in pregnancy, postpartum depression in a mother choosing to breast-feed, and depression related to perimenopause/menopause. METHOD: After reviewing the literature and convening a work group of leading experts, we prepared a written survey covering a total of 858 treatment options in 117 specific clinical situations. Depression severity (mild to severe) was specified for most clinical situations. Treatment options included a broad range of pharmacological, psychosocial, and alternative medicine approaches. Most options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. We identified 40 national experts, 36 (90%) of whom completed the survey. Consensus on each option was defined as a non-random distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred choice, second line/alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on 76% of the options, with greater consensus in situations involving severe symptoms. For women with severe symptoms in each of the 4 central disorder areas we asked about, the first-line recommendation was for antidepressant medication combined with other modalities (generally psychotherapy), paralleling existing guidelines for severe depression in general populations. For milder symptoms in each situation, the panel was less uniform in recommending antidepressants. For the initial treatment of milder symptoms, the panel either gave equal endorsement to other treatment modalities (e.g., nutritional or psychobehavioral approaches in PMDD; hormone replacement in perimenopause) or preferred psychotherapy over medication (in conception, pregnancy, or lactation). In all milder cases, however, antidepressants were recommended as at least second-line options. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) as a class were recommended as first-line treatment in all situations. The specific SSRIs that were preferred depended on the particular clinical situation. Tricyclic antidepressants were highly rated alternatives to SSRIs in pregnancy and lactation. CONCLUSIONS: The experts reached a high level of consensus on the appropriateness of including both antidepressant medication, specifically SSRIs, and nonpharmacological modalities in treatment plans for severe depression in 4 key clinical situations unique to women. To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data in comparing modalities with each other or in combination. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in women. They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions.

Allen MH, Currier GW, Hughes DH, Reyes-Harde M, Docherty JP, Anonymous00290. · University of Colorado School of Medicine, USA. · Postgrad Med. · Pubmed #11500996 No free full text.

Abstract: OBJECTIVES: Behavioral emergencies are a common and serious problem for consumers, their communities, and the healthcare settings on which they rely to contain, assess, and ultimately help the individual in a behavioral crisis. Partly because of the inherent dangers of this situation, there is little research to guide provider responses to this challenge. Key constructs such as agitation have not been adequately operationalized so that the criteria defining a behavioral emergency are vague. The significant progress that has been made for some disease states with better treatments and higher consumer acceptance has not penetrated this area of practice. A significant number of deaths of patients in restraint has focused government and regulators on these issues, but a consensus about key elements in the management of behavioral emergencies has not yet been articulated by the provider community. The authors assembled a panel of 50 experts to define the following elements: the threshold for emergency interventions, the scope of assessment for varying levels of urgency and cooperation, guiding principles in selecting interventions, and appropriate physical and medication strategies at different levels of diagnostic confidence and for a variety of etiologies and complicating conditions. METHOD: In order to identify issues in this area on which there is consensus, a written survey with 808 decision points was developed. The survey was mailed to a panel of 52 experts, 50 of whom completed it. A modified version of the RAND Corporation 9-point scale for rating appropriateness of medical decisions was used to score options. Consensus on each option was defined as a non-random distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred choice, second line/alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables were constructed describing the preferred strategies in key clinical situations. RESULTS: The expert panel reached consensus on 83% of the options. The relative appropriateness of emergency interventions was ascertained for a continuum of behaviors. When asked about the frequency with which emergency interventions (parenteral medication, restraints, seclusion) were required in their services, 47% of the experts reported that such interventions were necessary for 1%-5% of patients seen in their services and 32% for 6%-20%. In general, the consensus of this panel lends support to many elements of recent Health Care Financing Administration regulations, including the timing of clinician assessment and reassessment and the intensity of nursing care. However, the panel did not endorse the concept of "chemical restraint," instead favoring the idea that medications are treatments for target behaviors in behavioral emergencies even when the causes of these behaviors are not well understood. Control of aggressive behavior emerged as the highest priority during the emergency; however, preserving the physician-patient relationship was rated a close second and became the top priority in the long term. Oral medications, particularly concentrates, were clearly preferred if it is possible to use them. Benzodiazepines alone were top rated in 6 of 12 situations. High-potency conventional antipsychotics used alone never received higher ratings than benzodiazepines used alone. A combination of a benzodiazepine and an antipsychotic was preferred for patients with suspected schizophrenia, mania, or psychotic depression. There was equal support for high-potency conventional or atypical antipsychotics (particularly liquids) in oral combinations with benzodiazepines. Droperidol emerged in fourth place in some situations requiring an injection. CONCLUSIONS: To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data in comparing modalities with each other or in combination. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in the management of psychiatric emergencies and can be used to inform clinicians in acute care settings regarding the relative merits of various strategies.

Sachs GS, Printz DJ, Kahn DA, Carpenter D, Docherty JP. · Partners Bipolar Treatment Center, Massachusetts General Hospital, USA. · Postgrad Med. · Pubmed #10895797 No free full text.

Abstract: OBJECTIVES: New treatments for bipolar disorder have been reported since we first published survey-based expert consensus guidelines in 1996. The evidence for these treatments varies widely; data are especially limited regarding comparisons between treatments and how to sequence them. We therefore undertook a new survey of expert opinion in order to bridge gaps between the research evidence and key clinical decisions. METHOD: Based on a literature review, a written survey was prepared which asked about 1,276 options for psychopharmacologic interventions in 48 specific clinical situations. Most options were scored using a modified version of the RAND Corporation 9-point scale for rating appropriateness of medical decisions. We contacted 65 national experts, 58 of whom (89%) completed the survey. Consensus on each option was defined as a non-random distribution of scores by chi-square test. We assigned a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) to each option based on the confidence interval of its mean rating. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on many key strategies, including acute and preventive treatment for mania (euphoric, mixed, and dysphoric subtypes), depression, and rapid cycling, and approaches to managing the complications of treatment resistance and comorbidity. Use of a mood stabilizer is recommended in all phases of treatment. Divalproex (especially for mixed or dysphoric subtypes) and lithium are the cornerstone choices among this class for both acute and preventive treatment of mania. Regardless of which is selected first, if monotherapy fails, the next recommended intervention is to use these agents in combination. The combination can then serve as the foundation on which other medications are added, if needed. Carbamazepine is the leading alternative mood stabilizer for mania. Expert opinion regards other new anticonvulsants as second-line options (e.g., if the previously mentioned mood stabilizers fail or are contraindicated). For milder depression, a mood stabilizer, especially lithium, may be used as monotherapy. Divalproex and lamotrigine are other first-line choices. For more severe depression, a standard antidepressant should be combined with lithium or divalproex. Bupropion, selective serotonin reuptake inhibitors (SSRIs), and venlafaxine are preferred antidepressants, and should be tapered 2 to 6 months after remission. Divalproex monotherapy is recommended for initial treatment of either depression or mania with rapid cycling. Antipsychotics are recommended for use with the above regimens for mania or depression with psychosis, and as potential adjuncts in non-psychotic episodes. Atypical antipsychotics, especially olanzapine and risperidone, were generally preferred over conventional antipsychotics. Recommendations are also given concerning the use of electroconvulsive therapy (ECT), clozapine, thyroid hormone, stimulants, and various novel agents for patients with treatment-refractory illness. CONCLUSIONS: The experts reached high levels of consensus on key steps in treating bipolar disorder despite obvious gaps in high-quality data. To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data; however, their recommendations are generally conservative. Experts reserve strongest support for initial strategies and individual medications for which there are high-quality research data, or for which there are longstanding patterns of clinical usage. Within the limits of expert opinion and with the understanding that new research data may take precedence, these guidelines provide clear pathways for addressing common clinical questions in a manner that can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions.

Alexopoulos GS, Streim J, Carpenter D, Docherty JP, Anonymous00411. · Cornell Institute of Geriatric Psychiatry and Weill Medical College of Cornell University, USA. · J Clin Psychiatry. · Pubmed #14994733 No free full text.

Abstract: OBJECTIVES: Antipsychotics are widely used in geriatric psychiatric disorders. A growing number of atypical antipsychotics are available, expanding clinical options but complicating decision-making. Many questions about use of antipsychotics in older patients remain unanswered by available clinical literature. We therefore surveyed expert opinion on antipsychotic use in older patients (65 years of age or older) for recommendations concerning indications for antipsychotics, choice of antipsychotics for different conditions (e.g., delirium, dementia, schizophrenia, delusional disorder, psychotic mood disorders) and for patients with comorbid conditions or history of side effects, dosing strategies, duration of treatment, and medication combinations. METHOD: Based on a literature review, a 47-question survey with 1,411 options was developed. Approximately three quarters of the options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For other options, experts were asked to write in answers. The survey was sent to 52 American experts on treatment of older adults (38 geriatric psychiatrists, 14 geriatric internists/family physicians), 48 (92%) of whom completed it. In analyzing responses to items rated on the 9-point scale, consensus was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred, second line/alternate, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean. Guidelines indicating preferred treatment strategies were then developed for key clinical situations. RESULTS: The expert panel reached consensus on 78% of options rated on the 9-point scale. The experts did not recommend using antipsychotics in panic disorder, generalized anxiety disorder, nonpsychotic major depression, hypochondriasis, neuropathic pain, severe nausea, motion sickness, or irritability, hostility, and sleep disturbance in the absence of a major psychiatric syndrome. However, antipsychotics were favored in several other disorders. For agitated dementia with delusions, the experts' first-line recommendation is an antipsychotic drug alone; they would also consider adding a mood stabilizer. Risperidone (0.5-2.0 mg/day) was first line followed by quetiapine (50-150 mg/day) and olanzapine (5.0-7.5 mg/day) as high second-line options. There was no first-line recommendation for agitated dementia without delusions; an antipsychotic alone was high second line (rated first line by 60% of the experts). The experts'first-line recommendation for late-life schizophrenia was risperidone (1.25-3.5 mg/day). Quetiapine (100-300 mg/day), olanzapine (7.5-15 mg/day), and aripiprazole (15-30 mg/day) were high second line. For older patients with delusional disorder, an antipsychotic was the only treatment recommended. For agitated nonpsychotic major depression in an older patient, the experts' first-line recommendation was an antidepressant alone (77% first line); second-line options were an antidepressant plus an antipsychotic, electroconvulsive therapy (ECT), an antidepressant plus a benzodiazepine, and an antidepressant plus a mood stabilizer. For nonpsychotic major depression with severe anxiety, the experts recommended an antidepressant alone (79% first line) and would also consider adding a benzodiazepine or mood stabilizer to the antidepressant. If an older patient with adequate dosages for adequate duration, there was limited support for adding an atypical antipsychotic to the antidepressant (36% first line after two failed antidepressant trials). Treatment of choice for geriatric psychotic major depression was an antipsychotic plus an antidepressant (98% first line), with ECT another first-line option (71% first line). For mild geriatric nonpsychotic mania, the first-line recommendation is a mood stabilizer alone; the experts would also consider discontinuing an antidepressant if the patient is receiving one. For severe nonpsychotic mania, the experts recommend a mood stabilizer alone; the experts would also consider discontinuing an antidepressant if the patient is receiving one. For severe nonpsychotic mania, the experts recommend a mood stabilizer plus an antipsychotic (57%; first line) or a mood stabilizer alone (48%; first line) and would discontinue any antidepressant the patient is receiving. For psychotic mania, treatment of choice is a mood stabilizer plus an antipsychotic (98%; first line). Risperidone (1.25-3.0 mg/day) and olanzapine (5-15 mg/day) were first-line options in combination with a mood stabilizer for mania with psychosis, with quetiapine (50-250 mg/day) high second line. If a patient has responded well, the experts recommended the following duration of treatment before attempting to taper and discontinue the antipsychotic: delirium, 1 week; agitated dementia, taper within 3-6 months to determine the lowest effective maintenance dose; schizophrenia, indefinite treatment at the lowest effective dose; delusional disorder, 6 months-indefinitely at the lowest effective dose; psychotic major depression, 6 months; and mania with psychosis, 3 months. For patients with diabetes, dyslipidemia, or obesity, the experts would avoid clozapine, olanzapine, and conventional antipsychotics (especially low- and mid-potency). Quetiapine is first line for a patient with Parkinson's disease. Clozapine, ziprasidone, and conventional antipsychotics (especially low- and mid-potency) should be avoided in patients with QTc prolongation or congestive heart failure. For patients with cognitive impairment, constipation, diabetes, diabetic neuropathy, dyslipidemia, xerophthalmia, and xerostomia, the experts prefer risperidone, with quetiapine high second line. More than a quarter of the experts considered these combinations contraindicated: clozapine + carbamazepine, ziprasidone + tricyclic antidepressant (TCA), and a low-potency conventional antipsychotic + fluoxetine. In combining antidepressants and antipsychotics, the experts would be much more cautious with selective serotonin reuptake inhibitors that are more potent inhibitors of the CYP 450 enzymes (i.e., fluoxetine, fluvoxamine, paroxetine) and with nefazodone, TCAs, and monoamine oxidase inhibitors. The experts recommended extra monitoring when combining any antipsychotic with lithium, carbamazepine, lamotrigine, or valproate (except aripiprazole, risperidone, or a high-potency conventional plus valproate) or with codeine, phenytoin, or tramadol. CONCLUSIONS: The experts reached a high level of consensus on many of the key treatment questions. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide direction for common clinical dilemmas in the use of antipsychotics in elderly patients. Clinicians should keep in mind that no guidelines can address the complexities of an individual patient and that sound clinical judgment based on clinical experience should be used in applying these recommendations.

Docherty JP, Sack DA, Roffman M, Finch M, Komorowski JR. · Comprehensive NeuroScience, Inc., White Plains, NY, USA. · J Psychiatr Pract. · Pubmed #16184071 No free full text.

Abstract: BACKGROUND:: In a small pilot trial, patients with atypical depression demonstrated significant positive therapeutic response to chromium picolinate. This finding is of interest because of the demonstrated link between depression, decreased insulin sensitivity, and subsequent diabetes and chromium picolinate's insulin enhancing effect. METHODS:: In this double-blind, multicenter, 8-week replication study, 113 adult outpatients with atypical depression were randomized 2:1 to receive 600 mug/day of elemental chromium, as provided by chromium picolinate (CrPic), or placebo. Primary efficacy measures were the 29-item Hamilton Depression Rating Scale (HAM-D-29) and the Clinical Global Impressions Improvement Scale (CGI-I). RESULTS:: Of the 113 randomized patients, 110 (70 CrPic, 40 placebo) constituted the intent-to-treat (ITT) population (i.e., received at least one dose of study medication and completed at least one efficacy evaluation) and 75 (50 CrPic, 25 placebo) were evaluable (i.e., took at least 80% of study drug with no significant protocol deviations). In the evaluable population, mean age was 46 years, 69% were female, 81% were Caucasian, and mean body mass index (BMI) was 29.7. There was no significant difference between the CrPic and placebo groups in both the ITT and evaluable populations on the primary efficacy measures, with both groups showing significant improvement from baseline on total HAM-D-29 scores during the course of treatment (p < 0.0001). However, in the evaluable population, the CrPic group showed significant improvements from baseline compared with the placebo group on 4 HAM-D-29 items: appetite increase, increased eating, carbohydrate craving, and diurnal variation of feelings. A supplemental analysis of data from the subset of 41 patients in the ITT population with high carbohydrate craving (26 CrPic, 15 placebo; mean BMI = 31.1) showed that the CrPic patients had significantly greater response on total HAM-D-29 scores than the placebo group (65% vs. 33%; p < 0.05) as well as significantly greater improvements on the following HAM-D-29 items: appetite increase, increased eating, carbohydrate craving, and genital symptoms (e.g., level of libido). Chromium treatment was well-tolerated. LIMITATIONS:: The study did not include a placebo run-in period, did not require minimum duration or severity of depression, and enrolled patients with major depression, dysthymia, or depression NOS. CONCLUSIONS:: In a population of adults with atypical depression, most of whom were overweight or obese, CrPic produced improvement on the following HAM-D-29 items: appetite increase, increased eating, carbohydrate craving, and diurnal variation of feelings. In a subpopulation of patients with high carbohydrate craving, overall HAM-D-29 scores improved significantly in patients treated with CrPic compared with placebo. The results of this study suggest that the main effect of chromium was on carbohydrate craving and appetite regulation in depressed patients and that 600 mug of elemental chromium may be beneficial for patients with atypical depression who also have severe carbohydrate craving. Further studies are needed to evaluate chromium in depressed patients specifically selected for symptoms of increased appetite and carbohydrate craving as well as to determine whether a higher dose of chromium would have an effect on mood.

Alexopoulos GS, Jeste DV, Chung H, Carpenter D, Ross R, Docherty JP. · No affiliation provided · Postgrad Med. · Pubmed #17203561 No free full text.

Abstract: OBJECTIVES: New treatment options for dementia and its behavioral disturbances have become available since publication of The Expert Consensus Guidelines on the Treatment of Agitation in Older Persons with Dementia in 1998. While only 2 cholinesterase inhibitors, donepezil and tacrine, were available in 1998, 3 new cognitive-enhancing agents have been introduced since that time as well as several new atypical antipsychotics and antidepressants. However, there are still limited data from controlled studies to guide clinicians in choosing among these agents and sequencing and combining treatments. We therefore conducted a new survey study of expert opinion on the treatment of cognitive impairment and behavioral disturbances associated with dementia. METHODS: Based on a literature review, a 61-question survey was developed with 1,225 options. Most options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions. For other options, the experts were asked to write in answers. The survey was sent to 50 North American experts on dementia, 100% of whom completed it. In analyzing responses to items rated on the 9-point scale, consensus was defined as a nonrandom distribution of scores by chi-square "goodness-of-fit" test. Based on the 95% confidence interval around the mean, we assigned a categorical rank (first line/preferred, second line/alternate, third line/usually inappropriate) to each option. Guidelines indicating preferred treatment strategies were then developed for selected clinical situations. RESULTS: For patients at risk for dementia, the experts recommended control of hypertension and diabetes. They also recommended aspirin and would consider a lipid-lowering agent in patients at risk for vascular dementia. Cholinesterase inhibitors were an option for patients with mild cognitive impairment (i.e., at risk for Alzheimer's dementia [AD]). To slow cognitive impairment in mild/moderate AD, the experts recommended a cholinesterase inhibitor alone or combined with vitamin E. Donepezil and galantamine were the preferred cholinesterase inhibitors. The experts recommended combining a cholinesterase inhibitor with a N-methyl-D-aspartate (NMDA) antagonist (e.g., memantine) if a patient with mild/moderate dementia has an inadequate response to monotherapy. Control of hypertension and diabetes was the treatment of choice, in patients with mild/moderate vascular or mixed AD/vascular dementia, with aspirin another first-line option. Cholinesterase inhibitors were also a first-line option for mild/moderate mixed AD/vascular dementia. Among nonpharmacological interventions for mild/moderate dementia, the experts recommended caregiver education, supportive therapy for caregivers, referral to day treatment, exercise programs, and respite care. For moderate/severe AD or mixed AD/vascular dementia, the experts recommended combining an NMDA antagonist with a cholinesterase inhibitor. For moderate/severe vascular or mixed AD/vascular dementia, they recommended control of hypertension and diabetes. The experts' ratings underscore the importance of nonpharmacological strategies aimed at reducing caregiver burden in more severe dementia. Management of agitation and other behavioral disturbances was another focus of this study. The experts recommended using an atypical antipsychotic for agitation associated with delirium, psychosis, aggression, or anger. They would also consider divalproex to manage anger with a risk of physical aggression. Selective serotonin reuptake inhibitors were recommended for the treatment of depression or anxiety in patients with dementia. Benzodiazepines or atypical antipsychotics were viewed as short-term options for acute anxiety. Trazodone was recommended for insomnia. The experts also gave recommendations concerning dosage levels, duration of treatment, and choice of medications for patients with different complicating conditions. CONCLUSIONS: The experts reached high levels of consensus on key steps in treating dementia and associated behavioral disturbances. Within the limits of expert opinion and with the expectation that new research data will take precedence, these guidelines may provide direction for clinicians offering care to patients with dementia.

Alexopoulos GS, Katz IR, Reynolds CF, Carpenter D, Docherty JP, Ross RW. · Cornell Institute of Geriatric Psychiatry, White Plains, NY 10605, USA. · J Psychiatr Pract. · Pubmed #15990550 No free full text.

Abstract: Depression in older adults increases disability, medical morbidity, mortality, suicide risk, and healthcare utilization. Most studies of antidepressants are conducted in younger adults, and clinicians often have to extrapolate from findings in populations that do not present the same problems as older patients. Older patients often have serious coexisting medical conditions that may contribute to or complicate treatment of depression; they tend to take multiple medications, some of which may contribute to depression or interact with antidepressants; and they metabolize medications slowly and are more sensitive to side effects than younger patients.To address clinical questions not definitively answered in the research literature, the authors surveyed 50 experts on the pharmacotherapy of depressive disorders in older patients. The survey contained 64 questions with 857 options: 618 of the options were scored using a modified version of the RAND 9-point scale for rating appropriateness of medical decisions; for the other 239 options, the experts were asked to write in answers or check a box. The experts reached consensus on 89% of the options rated on the 9-point scale. Categorical rankings (first line/preferred, second line/alternate, third line/usually inappropriate) were assigned to each option based on the 95% confidence interval around the mean rating. Guideline tables indicating preferred treatment strategies were then developed for common and important clinical scenarios.The authors summarize the expert consensus methodology and the experts' recommendations and discuss how they relate to research findings. The experts recommend including both antidepressant medication and psychotherapy in treatment plans for nonpsychotic unipolar major depressive disorder of any severity, as well as for dysthymic disorder or persistent minor depressive disorder. They would also consider using either medication or psychotherapy alone for milder depression. For unipolar psychotic major depression, the treatment of choice is an antidepressant plus one of the newer atypical antipsychotics, with electroconvulsive therapy another first-line option. If the patient has a comorbid medical condition that is contributing to the depression, the experts recommend treating both the depression and the medical condition from the outset.The SSRIs were the top-rated antidepressants for all types of depression, with highest ratings for efficacy and tolerability given to citalopram and sertraline. Paroxetine was another first-line option, and fluoxetine was rated high second line. The preferred psychotherapy techniques for treating depression in older patients are cognitive-behavioral therapy, supportive psychotherapy, problem-solving psychotherapy, and interpersonal psychotherapy. The experts also recommended use of psychosocial interventions (e.g., psychoeducation, family counseling, visiting nurse services) in addition to pharmacotherapy and psychotherapy.Within limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide direction concerning common clinical dilemmas in older patients. They cannot address the complexities of each individual patient's care and can be most helpful in the hands of experienced clinicians.

Altshuler LL, Cohen LS, Moline ML, Kahn DA, Carpenter D, Docherty JP, Ross RW. · UCLA Neuropsychiatric Institute and VA Greater Los Angeles Healthcare Systems, USA. · J Psychiatr Pract. · Pubmed #15990522 No free full text.

Abstract: Women constitute two-thirds of patients suffering from common depressive disorders, making the treatment of depression in women a substantial public health concern. However, high-quality, empirical data on depressive disorders specific to women are limited, and there are no comprehensive evidence-based practice guidelines on the best treatments for these illnesses. To bridge the gap between research evidence and key clinical decisions, the authors developed a survey of expert opinion concerning treatment of four depressive conditions specific to women: premenstrual dysphoric disorder, depression in pregnancy, postpartum depression in a mother choosing to breast-feed, and depression related to perimenopause/menopause. The survey asked about 858 treatment options in 117 clinical situations and included a broad range of pharmacological, psychosocial, and alternative medicine approaches. The survey was sent to 40 national experts on women's mental health issues, 36 (90%) of whom completed it. The options, scored using a modified version of the RAND Corporation's 9-point scale for rating appropriateness of medical decisions, were assigned one of three categorical rankings-first line/preferred choice, second line/alternate choice, third line/usually inappropriate-based on the 95% confidence interval of each item's mean rating. The expert panel reached consensus (defined as a non-random distribution of scores by chi-square "goodness-of-fit" test) on 76% of the options, with greater consensus in situations involving severe symptoms. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations.The authors summarize the expert consensus methodology they used and then, for each of the four key areas, review the treatment literature and summarize the experts' recommendations and how they relate to the research findings. For women with severe symptoms in each area we asked about, the first-line recommendation was antidepressant medication combined with other modalities (generally psychotherapy). These recommendations parallel existing guidelines for severe depression in general populations. For initial treatment of milder symptoms in each situation, the panel was less uniform in recommending antidepressants, and either gave equal endorsement to other treatment modalities (e.g., nutritional or psychobehavioral approaches in PMDD; hormone replacement in perimenopause) or preferred psychotherapy over medication (during conception, pregnancy, or lactation). In all milder cases, however, antidepressants were recommended as at least second-line options. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) were recommended as first-line treatment in all situations. The specific SSRIs that were preferred depended on the particular clinical situation. Tricyclic antidepressants were highly rated alternatives to SSRIs in pregnancy and lactation.In evaluating many of the treatment options, the experts had to extrapolate beyond controlled data in comparing treatment options with each other or in combination. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in women, and can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions.

Kahn DA, Sachs GS, Printz DJ, Carpenter D, Docherty JP, Ross R. · Columbia University, USA. · J Psychiatr Pract. · Pubmed #15990485 No free full text.

Abstract: The original Expert Consensus Guidelines on the Treatment of Bipolar Disorder were published in 1996. Since that time, a variety of new treatments for bipolar disorder have been reported; however, evidence for these treatments varies widely, with data especially limited regarding comparisons between treatments and how to sequence them. For this reason, a new survey of expert opinion was undertaken to bridge gaps between the research evidence and key clinical decisions. The results of this new survey, which was completed by 58 experts, are presented in The Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder 2000, which was published in April 2000 as a Postgraduate Medicine Special Report. In this article, the authors describe the methodology used in the survey and summarize the clinical recommendations given in the resulting guidelines. The expert panel reached consensus on many key strategies, including acute and preventive treatment of mania (euphoric, mixed, and dysphoric subtypes), depression, rapid cycling, and approaches to managing treatment resistance and comorbid psychiatric conditions. Use of a mood stabilizer is recommended in all phases of treatment. Divalproex (especially for mixed or dysphoric subtypes) and lithium are the primary mood stabilizers for both acute and preventive treatment of mania. If monotherapy with these agents fails, the next recommended intervention is to combine them. This combination of lithium and divalproex can then serve as the foundation to which other medications are added if needed. Carbamazepine is the leading alternative mood stabilizer for mania. The experts rated the other new anticonvulsants as second-line options (i.e., their use is recommended if lithium, divalproex, and carbamazepine fail or are contraindicated). For milder depression, a mood stabilizer, especially lithium, may be used as monotherapy. Divalproex and lamotrigine are other first-line choices. For more severe depression, the experts recommend combining a standard antidepressant with lithium or divalproex. Bupropion, selective serotonin reuptake inhibitors (SSRIs), and venlafaxine are preferred antidepressants. The antidepressants should usually be tapered 2-6 months after remission. Monotherapy with divalproex is recommended for the initial treatment of either depression or mania in rapid-cycling bipolar disorder. Antipsychotics are recommended for use in combination with the above regimens for mania or depression with psychosis, and as potential adjuncts in nonpsychotic episodes. Atypical antipsychotics, especially olanzapine and risperidone, were generally preferred over conventional antipsychotics. The guidelines also include recommendations concerning the use of electroconvulsive therapy (ECT), clozapine, thyroid hormone, stimulants, and various novel agents for patients with treatment-refractory bipolar illness. The experts reached high levels of consensus on key steps in treating bipolar disorder despite obvious gaps in high-quality data. To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data; however, their recommendations are generally conservative. Experts give their strongest support to initial strategies and medications for which high-quality research data or longstanding patterns of clinical usage exist. Within the limits of expert opinion and with the understanding that new research data may take precedence, these guidelines provide clear pathways for addressing common clinical questions and can be used to inform clinicians and educate patients about the relative merits of a variety of interventions.

Allen MH, Currier GW, Hughes DH, Docherty JP, Carpenter D, Ross R. · University of Colorado School of Medicine, USA. · J Psychiatr Pract. · Pubmed #15985913 No free full text.

Abstract: OBJECTIVES: Behavioral emergencies are a common and serious problem for consumers, their communities, and the healthcare settings on which they rely, but there is little research to guide provider responses to this challenge. Key constructs such as agitation have not been adequately operationalized so that the criteria defining a behavioral emergency are vague. A significant number of deaths of patients in restraint has focused government and regulators on these issues, but a consensus about key elements in the management of behavioral emergencies has not yet been articulated by the provider community. The authors assembled a panel of 50 experts to define the following elements: the threshold for emergency interventions, the scope of assessment for varying levels of urgency and cooperation, guiding principles in selecting interventions, and appropriate physical and medication strategies at different levels of diagnostic confidence and for a variety of etiologies and complicating conditions. METHOD: A written survey with 808 decision points was completed by 50 experts. A modified version of the RAND Corporation 9-point scale for rating appropriateness of medical decisions was used to score options. Consensus on each option was defined as a non-random distribution of scores by chi-square "goodness-of-fit" test. We assigned a categorical rank (first line/preferred choice, second line/ alternate choice, third line/usually inappropriate) to each option based on the 95% confidence interval around the mean rating. Guideline tables were constructed describing the preferred strategies in key clinical situations. RESULTS: The expert panel reached consensus on 83% of the options. The relative appropriateness of emergency interventions was ascertained for a continuum of behaviors. When asked about the frequency with which emergency interventions (parenteral medication, restraint, seclusion) were required in their services, 47% of the experts reported that such interventions were necessary for 1%-5% of patients seen in their services and 32% for 6%-20%. In general, the consensus of this panel lends support to many elements of recent regulations from the Health Care Financing Administration (now the Centers for Medicare and Medicaid Services), including the timing of clinician assessment and reassessment and the intensity of nursing care. However, the panel did not endorse the concept of "chemical restraint," instead favoring the idea that medications are treatments for target behaviors in behavioral emergencies even when the causes of these behaviors are not well understood. Control of aggressive behavior emerged as the highest priority during the emergency; however, preserving the physician-patient relationship was rated a close second and became the top priority in the long term. Oral medications, particularly concentrates, were clearly preferred if it is possible to use them. Benzodiazepines alone were top rated in 6 of 12 situations. High-potency conventional antipsychotics used alone never received higher ratings than benzodiazepines used alone. A combination of a benzodiazepine and an antipsychotic was preferred for patients with suspected schizophrenia, mania, or psychotic depression. There was equal support for high-potency conventional or atypical antipsychotics (particularly liquids) in oral combinations with benzodiazepines. Droperidol emerged in fourth place in some situations requiring an injection. CONCLUSIONS: To evaluate many of the treatment options in this survey, the experts had to extrapolate beyond controlled data. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in the management of psychiatric emergencies and can be used to inform clinicians in acute care settings regarding the relative merits of various strategies.