Guiding Principles of The Texas Implementation of Medication Algorithms (TIMA)

Algorithms were developed after examining the quality and quantity of efficacy data, expert opinion, consumer input, and safety and tolerability issues. Certain treatment options were placed lower in the algorithm due to concerns about safety and tolerability, despite strong efficacy evidence,

These algorithms were intended to provide systematic guidance on possible treatment options for BDI. Medication guidelines should be used to help the clinician and patient develop the most effective medication strategy with the fewest side effects, and are not meant to be rigid or choice-limiting. Although it is recommended that the algorithms be followed as linearly as possible, these guidelines are meant to provide flexibility at each stage of choosing treatments for each patient. The main goals of the algorithms are symptomatic remission, full return of psychosocial functioning, and prevention of relapse and recurrence.  Printer- Friendly Email This

Medscape Psychiatry & Mental Health.  2006;11(1) ©2006 Medscape
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New Views of Disease-Modifying Antirheumatic Drug Therapy

from Topics in Advanced Practice Nursing eJournal

Signs and Symptoms

RA may present insidiously or with the onset of polyarthritis. The typical patient with RA has vague arthralgias, morning stiffness, and fatigue. In some patients, the onset is more acute, with inflammation of the wrists, the proximal interphalangeals (PIP), metacarpophalangeals (MCP), or metatarsophalangeal (MTP) joints that persists beyond 6 weeks.[3]

The American College of Rheumatology has developed a list of diagnostic criteria for RA:[4]

Morning stiffness in joints lasting at least 1 hour

Pain and swelling in at least 3 joints

Swelling in the wrist or MCP or PIP joint

Symmetrical involvement of joints

Subcutaneous nodules over bony prominences

Positive serum rheumatoid factor

Periarticular osteopenia or erosions in joints visible on radiographic examination of hands or feet

According to the American Rheumatism Association,[4] confirmation of 4 or more of these criteria is necessary to establish a diagnosis of RA. Joint symptoms are caused by inflammatory synovitis, which presents as erythema, warmth, and swelling of the joint area.

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July 7, 2004 — Patients treated with an algorithm-based program for major depressive disorder (MDD) had better outcomes than those treated with usual care, according to the results of a prospective trial published in the July issue of the Archives of General Psychiatry.

"Because no one treatment is a panacea, clinicians often use a sequence of treatment steps (either monotherapies or combinations) to increase the likelihood of response or remission," write Madhukar H. Trivedi, MD, from the University of Texas Southwestern Medical Center in Dallas, and colleagues. "Decision tree-based algorithms hold the promise of increased consistency of treatment across practitioners, which in turn should lead to better clinical outcomes and more efficient use of health care resources."

The Texas Medication Algorithm project compared algorithm-guided treatment (ALGO) for MDD with treatment as usual (TAU) in four ALGO clinics, six TAU clinics, and four clinics offering TAU to patients with MDD but ALGO to patients with schizophrenia or bipolar disorder.

Outpatients with MDD were divided into ALGO and TAU groups. The ALGO group included patients who were starting antidepressant therapy or who needed a change of antidepressant medication. The TAU group initially met the same criteria. Because medication changes were less frequent in the TAU group, patients were also recruited if their Brief Psychiatric Rating Scale (BPRS) total score was higher than the median for that clinic's routine quarterly evaluation of each patient.

All patients improved during the one-year study (P < .001). However, ALGO patients had significantly greater symptom reduction than TAU patients on the 30-item Inventory of Depressive-Symptomatology Clinician Rated (IDS-C30) scale, the 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR30) scale, and 12-item Short-Form Health Survey (SF-12) mental health score (P = .046).

Study limitations include lack of randomization, lack of blinding of the outcome assessors, and varying degrees of algorithm adherence.

"The ALGO intervention package during one year was superior to TAU for patients with MDD based on clinician-rated and self-reported symptoms and overall mental functioning," the authors write. "At the practitioner level, we need to explore mechanisms to increase algorithm adherence, including academic detailing, continuous quality improvement, and computerized decision support systems."

The National Institutes of Mental Health and various governmental agencies, pharmaceutical companies, and private foundations supported this project and some of its investigators.

Arch Gen Psych. 2004;61:669-680

Learning Objectives for This Educational Activity

Upon completion of this activity, participants will be able to: Describe components of the ALGO vs. TAU intervention for patients with MDD.Compare the effect of the ALGO intervention with TAU in an outpatient psychiatric setting.

Clinical Context

MDD affects 7% to 12% of men and 20% to 25% of women in their lifetime. Ten percent to 30% of those with MDD have a chronic course with episodes that last two or more years. MDD accounts for up to 60% of psychiatric hospitalizations and 8% to 15% of patients commit suicide. Patients in the U.S. public mental health sector tend to have severe symptoms, poor daily functioning, concurrent medical conditions, and alcohol and other substance abuse. Undertreatment is common and adherence to therapy is a problem. Efficacy trials indicate that one third of patients respond to medications with remission in six to eight weeks with higher remission rates in longer trials. One study by Hirschfield and colleagues published in the September 2001 issue of the British Journal of Psychiatry reported that in the longer term 10% to 30% of patients who do not respond to initial treatment, subsequently, develop depressive relapses within four to six months. Few studies have addressed the optimal management of patients with unsatisfactory clinical responses.

The authors of this descriptive longitudinal study offered an ALGO intervention compared with the TAU approach to MDD patients in the public health mental sector attending 14 psychiatric outpatient clinics to examine the one-year impact on clinician and patient-rated depression and quality-of-life outcomes.

ALGO is an enriched disease-management model that includes a set of physician protocols addressing medication management (using a manual, didactic training, and biweekly telephone expert consultation), on-site clinical coordinator support for patient services, patient and family education program with a manual for the patient, for MDD patients with and without psychosis. Decision points are at weeks 4, 6, 8, 10, and 12. Goals are to enhance adherence and optimal medication selection and dosage with minimal adverse-effect burden.

Study Highlights

Patients from 4 clinics offering ALGO were compared with those from 6 clinics offering TAU only and 4 offering ALGO to patients with schizophrenia and bipolar disorder but not MDD patients for one year.8 of 14 clinics were rural in setting. Ethnicity was described as 12% to 90% white, 2% to 86% Hispanic, and 0.3% to 58% black across the 14 clinics.Inclusion criteria were older than 18 years, psychotic or nonpsychotic MDD requiring medication change, starting antidepressant therapy, or higher than median BPRS-24 score.Exclusion criteria were schizophrenia, bipolar disorder, mental retardation, or primary diagnosis of obsessive compulsive or eating disorder and inpatient detoxification at time of study.Both groups had equal access to the same medications. The TAU group received nonprotocol-driven usual care as determined by patient needs at each visit.Physician adherence to ALGO protocols was not reported. Assessors of outcomes were not blinded to assignment.Primary outcome was change in clinician-assessed IDS-C30 score. A 4.4-point difference in this score is equivalent to a 3-point difference on the Hamilton Rating Scale for Depression.Secondary outcomes were IDS-SR30, BPRS-24, patient-rated health-related quality of life using the SF-12-Mental Health Summary and Patient Perception of Benefits instrument, and burden of adverse effects.Percentage of patients available for analyses were 100% at 3 months, 99.5% at 6 months, 83.2% at 9 months, and 75.9% at 12 months. The analytic sample (intent-to-treat) consisted of 175 in the ALGO and 175 in the TAU groups.Both groups had significant declines in IDS-C30 scores, and the decline was significantly greater for ALGO than TAU patients in the first 3 months. The magnitude of difference was 4.5 points.On the IDS-SR30, there was also significantly greater symptom reduction associated with the ALGO group compared with the TAU group, with a magnitude difference of 7.5 points between the two groups.The benefits in the ALGO group for both outcomes were accounted for by patients with very severe and severe baseline IDS-C30 scores and worse functioning as indicated by the SF-12 score.By clinician rating, twice as much symptom reduction occurred with ALGO as with TAU. By patient-rating, three times as much benefit was noted by the ALGO group.Mental functioning by the SF-12- Mental Health Summary instrument improved significantly more with the ALGO than the TAU group, with no discernable catch up by the TAU group for one year.Even among responders, substantial symptoms remained at the end of one year.Differences in growth rates in adverse effects during follow-up were not significantly different.

Pearls for Practice

The ALGO intervention model for patients with MDD included a set of physician protocols addressing medication management, on-site clinical coordinator support for patient services, and patient and family education program with a manual for the patient. The TAU group received nonprotocol-driven usual care for MDD as determined by patient needs at each visit.The ALGO intervention for one year is associated with significantly better clinician and patient-reported symptom control, therapy adherence, and quality of life compared with TAU for MDD patients in the public sector.
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Cost Studies in Rheumatology, 2001-2002

from Current Opinion in Rheumatology

Management of Infected Total Joint Replacement

Fisman et al.[9] performed an excellent study examining the cost-effectiveness of two-stage exchange arthroplasty and open debridement with prosthesis retention in elderly patients with infected total hip arthroplasty. Lifetime direct medical costs as well as indirect costs from loss of productivity were assessed using a Markov model. Incremental ratios demonstrated that when compared with exchange arthroplasty, initial debridement and retention had lower cost-effectiveness ratios ($500-$21,800/QALY) in all cohorts regardless of gender.

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Results

Of the 284 articles identified from the initial search strategy, only 12 met the study criteria (Figure 1). Three additional studies were found in a search undertaken in September 2003. No further studies were found in December 2004. There were 890 participants in SSRI studies, 596 in TCA studies, and 1,267 patients on placebo ( Table 1 ).[16–30] Of the 5 possible SSRIs available, 2 studied sertraline, 3 studied escitalopram (a precursor of citalopram), and 1 studied citalopram. Of the TCAs available, 2 studied dothiepin, 4 studied amitriptyline, 2 studied mianserin, and 3 studied imipramine. Ten of the 15 studies were identified as having a competing interest.

Figure 1.  (click image to zoom)

Number of studies from the initial search (12 from the initial search and 3 from the updated search)      

Our Results confirm that both TCA and SSRI are significantly effective compared with placebo (Figures 2 and 3). For depression scores the standardized mean difference for TCA vs placebo was –0.42 (95% confidence interval [CI], –0.55 to –0.3). The relative risk for improvement using TCA medications was 1.26 (95% CI, 1.12 to 1.42). For SSRI medications the relative risk for improvement was 1.37 (95% CI, 1.21 to 1.55). The number needed to treat for 1 improved patient ranged from 3 to 4 for the TCA studies that were statistically significant. Likewise, the number needed to treat was 6 for SSRIs. We performed an analysis with 5 studies (not shown) that had treatment group scores of <8 on the HAMD. The weighted mean difference was –3.68 (95% CI, –5.89 to –1.47). There was no significant heterogeneity for any analyses, so a fixed effects analysis was used. No significant differences were found for those studies in which means were approximated from graphs or standard errors were assumed from other studies compared with studies that had published data. A funnel plot of the TCA studies suggested that small studies with a small effect size might be missing (the funnel plot is not shown). The funnel plot methodology gives a qualitative view of publication bias but not a quantitative perspective and is therefore difficult to interpret.

Figure 2.  (click image to zoom)

Tricyclic vs placebo for improvement.      

Figure 3.  (click image to zoom)

SSRI vs placebo for improvement.      

The relative risk for adverse effects leading to study withdrawal for TCAs was 2.35 (95% CI, 1.59 to 3.46) (Figure 4) and for SSRIs the relative risk was 2.01 (95% CI, 1.1 to 3.7) (Figure 5). The number needed to harm in terms of study withdrawal resulting from adverse effects for 2 statistically significant TCA studies was 5 and 10. None of the 4 SSRI studies had statistically significant findings for adverse effects leading to withdrawal, but using the pooled figure and the range of baseline risks, the number needed to harm ranged from 21 to 94.

Figure 4.  (click image to zoom)

Tricyclic vs placebo for adverse effects leading to withdrawal.      

Figure 5.  (click image to zoom)

SSRI vs placebo for adverse effects leading to withdrawal.      

Seven studies did not meet the minimum quality criteria on at least 1 of the key components of methodological quality.[18,22,25,27–29] A score of 0 on any component caused the study to be rated as being poor quality. Only 4 studies used an intention-to-treat analysis, and these studies were the most recent. When studies of low methodological quality for the TCAs (n = 6) were removed from analysis, the pooled standardized mean difference or depression score for TCA vs placebo was –0.50 (95% CI, –0.65 to –0.35). For improvement for the TCAs the relative risk was 1.34 (95% CI, 1.16to 1.55). When studies in which at least one half of its assessors were family practitioners were pooled, the standardized mean difference was –0.43 (95% CI, –0.58 to –0.28) and the relative risk was 1.2 (95% CI, 1.03 to 1.4). There were sufficient data to assess continuous outcomes for TCAs at 1 week, 2 weeks, and 4 weeks. The standardized mean difference at 1 week was –0.02 (95% CI, –0.17 to 0.13), at 2 weeks it was –0.2 (95% CI, –0.36 to –0.04), and at 4 weeks it was –0.34 (95% CI, –0.5 to –0.18). For studies that used a HAMD <8 as an outcome (considered to be a remission) the weighted mean difference was –3.68 (95% CI, –5.89 to –1.47). For the 3 studies that reported no conflict of interest, the weighted mean difference was –4.59 (95% CI, –6.82 to 2.36).

Ten studies included an arm with 100 mg or more of a tricyclic antidepressant or more than 60 mg of mianserin. For the 10 studies in which a high dose was given, the standardized mean difference was –0.42 (95% CI, –0.56 to –0.29). The relative risk for these studies was 1.32 (95% CI, 1.15 to 1.5). For the 4 studies of tricyclic antidepressants using a dose of 100 mg/d or less, the weighted mean difference (all used the HAMD) was –3.15 (95% CI, –5.05 to –1.24). For the 2 studies of tricyclic antidepressants using a dose of 75 mg/d, the weighted mean difference was –3.93 (95% CI, –7.65 to –0.21).

Most studies had heterogeneous diagnoses in their participants. Only 2 TCA studies had major depressive disorder as the single diagnosis, and the weighted mean difference for that study was –1.37 (95% CI, –2.52 to –0.22).[19,29] For the SSRI studies there were 4 studies in which all participants had major depressive disorder.[16,18,19,30] Only 3 of the 4 studies had data suitable for pooling, and the relative risk was 1.39 (95% CI, 1.21 to 1.61).  Printer- Friendly Email This

Ann Fam Med.  2005;3(5):449-456.  ©2005 Annals of Family Medicine, Inc.
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