David N. Osser

A 2012 Evidence-Based Algorithm for the Pharmacotherapy for Obsessive-Compulsive Disorder

There is a need to synthesize the growing body of literature on the pharmacotherapeutic management of patients with obsessive-compulsive disorder for clinicians working at a primary care level. We have aimed to generate a simple, easy-to-follow algorithm for the primary care practitioner. This seven-step algorithm addresses diagnosis of obsessive-compulsive disorder, initiation of pharmacotherapy, monitoring and maintenance treatment, and guidelines for the management of patients who are resistant to initial therapy. In creating this algorithm, we have drawn on the body of published evidence, as well as on expert opinion.

The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An Update on Posttraumatic Stress Disorder

Background: This project aimed to provide an organized, sequential, and evidence‐supported approach to the pharmacotherapy of posttraumatic stress disorder (PTSD), following the format of previous efforts of the Psychopharmacology Algorithm Project at the Harvard South Shore Program. Method: A comprehensive literature review was conducted to determine the best pharmacological choices for PTSD patients and to update the last published version (1999) of the algorithm. We focused on optimal pharmacological interventions to address the prominent symptoms of PTSD, with additional attention to the impact that common comorbidities have on treatment choices. Results: We found that SSRIs and SNRIs are not as effective as previously thought, and that awareness of their long‐term side effects has increased. New evidence suggests that addressing fragmented sleep and nightmares can improve symptoms (in addition to insomnia) that are frequently seen with PTSD (e.g., hyperarousal, reexperiencing). Prazosin and trazodone are emphasized at this initial step; if significant PTSD symptoms remain, an antidepressant may be tried. For PTSD‐related psychosis, an antipsychotic may be added. In resistant cases, two or three antidepressants may be used in sequence. Following that, or with partial improvement and residual symptomatology, augmentation may be tried; the best options are antipsychotics, clonidine, topiramate, and lamotrigine. Conclusion: This heuristic may be helpful in producing faster symptom resolution, fewer side effects, and increased compliance.

A psychopharmacological treatment algorithm for generalised anxiety disorder (GAD)

Generalised anxiety disorder (GAD) is defined as excessive and uncontrollable worry and anxiety about everyday life situations. It is a chronic disorder, and is associated with substantial somatisation, high rates of comorbid depression and other anxiety disorders, and significant disability. The evidence base for pharmacotherapy and psychotherapy has continued to grow, and a wide range of drug choices for GAD now exists. Current guidelines for GAD generally restrict themselves to presentation of the evidence for various treatments, which, as a result, generally do not offer detailed discussion or recommendation of strategies beyond the first level of treatment, or take into account the individual circumstances of the patient. Thus, there is a lack of algorithm-based treatment guidelines for GAD. Our aim is, therefore, to present an algorithm for the psychopharmacologic management of GAD, intended for all clinicians who treat patients with GAD, where issues of pharmacotherapy are under consideration. We also hope that these GAD algorithms and other guidelines can help to identify high-priority areas that need further study. In this algorithm, we provide a sequenced approach to the pharmacotherapy of GAD, taking into account salient symptomatology and comorbidity, levels of evidence and extent of response. Special issues, including comorbidity, insomnia, suicidality, substance abuse, treatment adherence, pregnancy and lactation, cross-cultural issues, use of medication in the elderly, psychosocial treatment and dosing issues are also addressed.

The Psychopharmacology Algorithm Project at the Harvard South Shore Program : An Update on Psychotic Depression

&NA; This new version of the psychotic depression algorithm has been developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The most effective treatment modality for inpatients with severe psychotic depression is electroconvulsive therapy. The first‐line psychopharmacological treatment is a combination of an antidepressant (either a tricyclic or a selective serotonin reuptake inhibitor) and an antipsychotic. If one of these combinations has failed, consider switching to the other. If both combinations have failed, the next psychopharmacological option would be to augment the combination with lithium. Another option, though with limited evidence, is monotherapy with clozapine. If there is a good reason to avoid combination therapy with an antipsychotic, then a trial of monotherapy with a TCA or an SSRI can be supported. If that fails, adding an antipsychotic or ECT should be considered.

A 2010 Evidence-Based Algorithm for the Pharmacotherapy of Social Anxiety Disorder

A growing evidence base on the management of social anxiety disorder has yielded many meta-analyses and guidelines on the pharmacotherapy of this clinically important condition. We aimed to update a pharmacotherapy algorithm for the treatment of social anxiety disorder that was developed to be concise and user friendly and that was addressed to the primary care practitioner in particular. The updated algorithm attempts to summarize succinctly the recent literature in this area, as well as to include the views of an international panel of experts with diverse experience. The algorithm comprises eight sequential steps, beginning with those focused on diagnosis and initiating treatment and ending with the management of the treatment-refractory patient.

The psychopharmacology algorithm project at the Harvard South Shore Program: an update on schizophrenia.

This article is an update of the algorithm for schizophrenia from the Psychopharmacology Algorithm Project at the Harvard South Shore Program. A literature review was conducted focusing on new data since the last published version (1999–2001). The first-line treatment recommendation for new-onset schizophrenia is with amisulpride, aripiprazole, risperidone, or ziprasidone for four to six weeks. In some settings the trial could be shorter, considering that evidence of clear improvement with antipsychotics usually occurs within the first two weeks. If the trial of the first antipsychotic cannot be completed due to intolerance, try another until one of the four is tolerated and given an adequate trial. There should be evidence of bioavailability. If the response to this adequate trial is unsatisfactory, try a second monotherapy. If the response to this second adequate trial is also unsatisfactory, and if at least one of the first two trials was with risperidone, olanzapine, or a first-generation (typical) antipsychotic, then clozapine is recommended for the third trial. If neither trial was with any these three options, a third trial prior to clozapine should occur, using one of those three. If the response to monotherapy with clozapine (with dose adjusted by using plasma levels) is unsatisfactory, consider adding risperidone, lamotrigine, or ECT. Beyond that point, there is little solid evidence to support further psychopharmacological treatment choices, though we do review possible options.

The psychopharmacology algorithm project at the Harvard South Shore Program: an algorithm for acute mania.

AbstractThis new algorithm for the pharmacotherapy of acute mania was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The authors conducted a literature search in PubMed and reviewed key studies, other algorithms and guidelines, and their references. Treatments were prioritized considering three main considerations: (1) effectiveness in treating the current episode, (2) preventing potential relapses to depression, and (3) minimizing side effects over the short and long term. The algorithm presupposes that clinicians have made an accurate diagnosis, decided how to manage contributing medical causes (including substance misuse), discontinued antidepressants, and considered the patient’s childbearing potential. We propose different algorithms for mixed and nonmixed mania. Patients with mixed mania may be treated first with a second-generation antipsychotic, of which the first choice is quetiapine because of its greater efficacy for depressive symptoms and episodes in bipolar disorder. Valproate and then either lithium or carbamazepine may be added. For nonmixed mania, lithium is the first-line recommendation. A second-generation antipsychotic can be added. Again, quetiapine is favored, but if quetiapine is unacceptable, risperidone is the next choice. Olanzapine is not considered a first-line treatment due to its long-term side effects, but it could be second-line. If the patient, whether mixed or nonmixed, is still refractory to the above medications, then depending on what has already been tried, consider carbamazepine, haloperidol, olanzapine, risperidone, and valproate first tier; aripiprazole, asenapine, and ziprasidone second tier; and clozapine third tier (because of its weaker evidence base and greater side effects). Electroconvulsive therapy may be considered at any point in the algorithm if the patient has a history of positive response or is intolerant of medications.

A systematic approach to the classification and pharmacotherapy of nonpsychotic major depression and dysthymia.

Nonpsychotic depressive and dysthymic states are reclassified and reorganized in order to maximize relevance to clinical psychopharmacology. In the initial phase of assessment, patients are divided into two easily recognized categories: moodnonreactive (autonomous) depression and mood-reactive depression. After family and past history of response and cost of drug are considered, a tricyclic antidepressant is usually selected for autonomous depression patients, and mood-reactive depression patients are initially given a serotonin reuptake inhibitor. Nonresponders from either category are changed to the alternative medication or have it added to their first drug. Nonresponders to both of these initial trials are then assessed for the presence of atypical depression symptoms by the Columbia criteria. If these symptoms are present, the patients may be offered a third medication trial with a monoamine oxidase inhibitor. Bupropion could be the choice if the monoamine oxidase inhibitor cannot be given expeditiously. This completes the initial assessment and treatment phase. Autonomous and mood-reactive patients who do not respond to this sequence of interventions are then reassessed for the presence of characterologic syndromes and comorbidity with some frequently encountered conditions. These may determine the choice of medication and the prognosis for a positive result from the next choices selected. When possible, specific recommendations are given for the various situations.

The Ascendancy of Second-Generation Antipsychotics as Frontline Antimanic Agents.

IntroductionKnowledge of the factors affecting the adoption of new medications can enhance mental health care and guide quality improvement and policy development. Food and Drug Administration indications for treating bipolar disorder with several second-generation antipsychotics (SGAs) in the 2000s represent an opportunity to identify factors that impact the spread of a then-innovative treatment through a new population. MethodsAnalysis of Department of Veterans Affairs administrative data identified the population of 170,811 veterans diagnosed with bipolar disorder from 2003 to 2010. We analyzed time trends and predictors of antimanic choice (SGA vs other) among the 40,512 outpatients with bipolar disorder who initiated their first VA outpatient antimanic prescription, using multinomial logistic regression in month-by-month analyses. We conducted classwise analyses and investigated prespecified predictors among specific agents. ResultsIn classwise analyses, SGAs supplanted lithium, valproate, and carbamazepine/oxcarbazepine as the most commonly initiated antimanics by 2007. Psychosis, but not other indices of severity, predicted SGA initiation. Demographic analyses did not identify substantial disparities in initiation of SGAs. Drug-specific analyses revealed some consideration of medical comorbidities in choosing among specific antimanic agents, although effect sizes were small. Most patients initiating an antimanic had received an antidepressant in the previous year. DiscussionSecond-generation antipsychotics quickly became the frontline antimanic treatment for bipolar disorder, although antidepressants most commonly predated antimanic prescriptions. Second-generation antipsychotics were used for a broad range of patients rather than being restricted to a severely ill subpopulation. The modest association of antimanic choice with relevant medical comorbidities suggests that continued attention to quality prescribing practices is warranted.

Patterns of initiation of second generation antipsychotics for bipolar disorder: a month-by-month analysis of provider behavior

BackgroundSeveral second generation antipsychotics (SGAs) received FDA approval for bipolar disorder in the 2000s. Although efficacious, they have been costly and may cause significant side effects. Little is known about the factors associated with prescribers’ decisions to initiate SGA prescriptions for this condition.MethodsWe gathered administrative data from the Department of Veterans Affairs on 170,713 patients with bipolar disorder between fiscal years 2003–2010. Patients without a prior history of taking SGAs were considered eligible for SGA initiation during the study (n =126,556). Generalized estimating equations identified demographic, clinical, and comorbidity variables associated with initiation of an SGA prescription on a month-by-month basis.ResultsWhile the number of patients with bipolar disorder using SGAs nearly doubled between 2003 and 2010, analyses controlling for patient characteristics and the rise in the bipolar population revealed a 1.2% annual decline in SGA initiation during this period. Most medical comorbidities were only modestly associated with overall SGA initiation, although significant differences emerged among individual SGAs. Several markers of patient severity predicted SGA initiation, including previous hospitalizations, psychotic features, and a history of other antimanic prescriptions; these severity markers became less firmly linked to SGA initiation over time. Providers in the South were somewhat more likely to initiate SGA treatment.ConclusionsThe number of veterans with bipolar disorder prescribed SGAs is rising steadily, but this increase appears primarily driven by a corresponding increase in the bipolar population. Month-by-month analyses revealed that higher illness severity predicted SGA initiation, but that this association may be weakening over time.