DESCRIPCIÓN DE LOS CRITERIOS UTILIZADOS EN LA ESCALA NOVA 5:

In recent years, ten studies have examined refill adherence patterns among

antidepressant users. The following section describes the studies that include either mental health specialty care or follow-up visits as covariates in predicting antidepressant adherence (Table 1.5).

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Table 1.5 Summary of Studies Examining Predictors of Antidepressant Adherence

Study Study population Sample size

Antidepressant use measure Identification of mental health specialty care Identification of optimal follow-up visits

Other significant predictors of antidepressant adherence

Akincigil, 20072

Commercially insured 2003-2005

4,312 Acute phase adherent: MPR>=75% during first 16 weeks after treatment initiation. Continuation phase adherent: MPR>=75% during week 17-33

Y

(significant)

N Older age, higher income, no headache or migraine, no CVD/diabetes, more number of medications excluding

psychotropics, newer-generation antidepressant, no other substance abuse

Whether patients filled their index antidepressant prescription (immediate non-adherence)

Y

(significant)

N Initial antidepressant type Bambauer,

200713

Commercially insured 2002-2004

11,878

Less than 52 days without antidepressant treatment during the 180-day episode of treatment was considered adherence

Y (not significant)

N Older age, no prior use of pain medication, treatment by multiple providers, antidepressant type. Busch,

200443 VA 2000-2001 27,713 At least 84 days (acute treatment phase), and 180 days _{(continuation phase) during a 180 days follow up period} Y (not _significant) N Older age, women, married _{patients, higher income, comorbid}

mental health diagnosis Charbonneau

, 20033

VA 1999 12,678 Refill adherence with MPR >79% during a fixed 3- month calendar profiling period (June 1, 1999 to August 31, 1999) was deemed adequate. The patient could be in acute, continuation, or maintenance phases.

Y

(significant)

N White race, married

Fairman, 199815

Commercially insured 1994-1995

3,101 Termination of antidepressant treatment before or on first month

Y (not significant)

N Older age, female, newer- generation antidepressant Hylan,

199916 Commercially _{insured 1993-1994} 1,034 Dichotomous. 1=had four or more prescriptions without _{switching or augmentation} Y _{(significant)} N Female, present of other mental _diseases

Jones, 20064 VA1997-2005 2,178 Refill adherence with MPR>=80% in 12 weeks was deemed adequate

Y (not significant)

Y

(significant)

Female, not married, higher number of medical or psychiatric comorbidities

Robinson, 20066

Commercially insured 2001-2004

60,386 Effective acute-phase treatment: at least 84 days of supply of antidepressant during the first 114 days. Effective continuation-phase treatment: at least 180 days of supply of antidepressant during the first 214 days.

Y

(significant)

N Newer-generation antidepressant, older age, female, higher wage, less medical comorbidity, capitated insurance Simon,

20017 Commercially _{insured 1994-1996} 369 Received at least 90 days of continuous antidepressant _{treatment at a minimally adequate dose} Y (not _significant) N -

Weilburg,

200317 Commercially _{insured 1996-1999} 1,550 Treatment adequacy was defined with at least one trial _{of an average daily dosage of 20mg fluoxetine}

equivalents of a period of 90 days

Y

(significant)

Ten studies examined adherence patterns in four ways: 1) early termination, 2) prescription refill count during follow-up period, 3) adherence during a fixed calendar

profiling period, and 4) adherence during guideline-concordant acute and continuation phases. Early termination

In a commercially insured population, Fairman et al.15 defined early termination of antidepressant if the length of therapy was less than 30 days. Receipt of an initial

antidepressant prescription from a non-psychiatrist was associated with a 28% increase in the odds of one-month termination compared to receipt from a psychiatrist, even though it was marginally statistically significant (p=0.052).15 Bambauer and colleagues examined factors predicting whether patients ever filled their index antidepressant prescription (immediate non-adherence).13 They found that being treated by a psychiatrist was associated with significantly lower odds of immediate non-adherence (OR=0.7, 95%CI: 0.61-0.8), while being treated by physician with other specialty was associated with significantly higher odds (OR=1.39, 95%CI: 1.22-1.6) compared with patients treated by primary care physicians. Prescription refill count during follow-up period

Hylan et al. found that the odds of receiving four or more antidepressant prescription refills in six months after initial diagnosis were significantly lower for patient initially seen during an office visit by a family practitioner, in other non-specialist healthcare clinic, and other acute care clinic compared with patient initially seen by a psychiatrist.16 Their measure

25 Adherence during a fixed calendar profiling period

In a VA sample, Charbonneau et al. defined duration adequacy as antidepressant refill adherence with medication possession ratio (MPR) >75% during a fixed 3-month calendar profiling period (June 1, 1999 to August 31, 1999). Because the antidepressant treatment period was cross-sectional, the profiling period could have been in acute, continuation, or maintenance phases of the treatment depending on a patient’s index diagnosis date. They found that receipt of care exclusively from a primary care clinic significantly reduced the probability of adequate antidepressant duration (OR=0.84, 95% CI: 0.72-0.94).3

Adherence during guideline-concordant acute/continuation phases

Three studies investigated adherence with a guideline-concordant acute phase4, 7, 17, and four studies examined both acute and continuation phases.2, 6, 13, 43 In a VA sample, Jones et al. defined antidepressant duration adequacy in acute phase if refill adherence had an MPR greater or equal to 80% in the first 12 weeks.4 They found that adequate outpatient follow-up (three or more during acute phase) was associated with increased odds for duration adequacy of acute phase antidepressant therapy (OR=2.1, 95% CI: 1.54-2.88), but initial diagnosis from mental health clinic was non-significant. This study included both optimal follow-up and location of initial diagnosis as covariates in the model predicting duration adequacy in acute phase. Simon and colleagues found that the proportion of patients receiving 90 days of continuous antidepressant therapy at minimally adequate dose was similar between primary care patients and patients initially treated by psychiatrists and patients initially treated by primary care providers.7 Weilburg et al. defined treatment adequacy as at least one trial of an average daily dosage of 20mg fluoxetine equivalents of a period of 90 days.17 Compared with patients receiving antidepressant prescriptions from primary care providers exclusively, they

found that the patients being cared by the following combination of providers were more likely to have adequate antidepressant treatment: primary care and other types of providers (OR=2.33, 95% CI: 1.56-3.48), psychiatrist exclusively (OR=2.64, 95% CI: 1.97-3.55), primary care and psychiatrist (OR=3.29, 95% CI: 1.99-5.51), psychiatrist and other type of providers (OR=5.04, 95% CI: 3.29-7.81), and primary care, psychiatrist, and other type of providers (OR=5.13, 95% CI: 2.86-9.61).

Busch et al., Bambauer et al., Akincigil et al, and. Robinson et al. conducted retrospective studies using HEDIS measures to define adherence in acute and continuation phases, which are most closely concordant with guideline recommendations.2, 6, 13, 43 Busch et al. examined whether veterans remained on antidepressant treatment for at least 84 days (acute treatment phase) and 180 days (continuation phase).43 They found that antidepressant adherence did not differ between patients treated in a mental health clinic and patients treated in a non-mental health clinic. Bambauer et al defined adherence as having less than 52 days without antidepressant treatment during the 180-day episode of treatment.13 They found that being initially prescribed by physicians with other specialty was associated with an increased risk of non-adherence (OR=1.4, 95% CI: 1.24-1.59) compared with patients treated by primary care physicians, but no differences were found between primary care physicians and psychiatrists. In addition, treatment by multiple providers was associated with lower odds of non-adherence (OR=0.83, 95% CI: 0.75-0.92). Akincigil et al. defined acute phase adherence

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psychiatrist was associated with higher odds of adherence in both the acute (OR=1.19, 95% CI: 1.03-1.38) and continuation phases (OR= 1.25, 95% CI: 1.02-1.53). Robinson et al. defined effective acute phase treatment as at least 84 days-of-supply of antidepressant during the first 114 days following initiation of the index antidepressant, and effective continuation phase treatment as at least 180 days-of-supply of antidepressant during the first 214 days following initiation of the index medication.6 They found that receipt of any mental health specialty care by a psychiatrist, mental health and chemical dependency treatment facility, psychologist, or psychiatric nurse significantly increased the odds of adherence in both the acute (OR=1.38, 95% CI: 1.33-1.43) and continuation phases (OR=1.46, 95% CI: 1.41-1.51).

In summary, five out of ten studies showed that patients with some form of contact with mental health specialists had better antidepressant adherence (Table 1.5). Several approaches have been used to evaluate antidepressant adherence. Studies using early termination might preclude inference beyond treatment initiation and measure based on prescription count is less precise without considering the days-of supply of each refill as well as the intervals between refills. Use of antidepressants can be more precisely estimated if the patients are followed when they initiate antidepressant treatment. The definition of provider specialty varied widely across prior studies. As discussed in 1.3.2.1, this dissertation used provider specialty based on index antidepressant as the source of information which gives a closer link to the actual provider who prescribed, and most likely, managed a patient’s antidepressant therapy. In addition, only one study included both mental health specialty care and follow-up visits as covariates in the regression model predicting antidepressant

provider effect with control over receipt of guideline-concordant outpatient follow-up visits during acute phase in a non-VA sample.