GUIDELINES ISSUED BY THE

THE PATIENT-PHYSICIAN RELATIONSHIP Discontinuation of Use and Switching of Antidepressants Influence of Patient-Physician Communication Scott A. Bull, PharmD X. Henry Hu, MD, MPH, PhD Enid M. Hunkeler, MA Janelle Y. Lee, MHA, DrPH Eileen E. Ming, ScD, MPH Leona E. Markson, ScD Bruce Fireman, MA GUIDELINES ISSUED BY THE Agency for Health Care Policy and Research and the American Psychiatric Association recommend continued treatment with antidepressants for at least 4 to 9 months after depressive symptoms resolve to prevent relapse. 1-3 Despite these guidelines, rates of treatment discontinuation within 3 months after the start of treatment can reach 68%, depending on the type of antidepressant prescribed and the population studied. 4-10 Drug-related adverse effects often cause patients to discontinue treatment, and efforts to improve the continuation of antidepressant use have yielded limited success. 11-15 A strong treatment alliance between physicians and patients that includes discussions about adverse effects throughout treatment may alleviate patients concerns and help them continue treatment. Moreover, intolerance to one antidepressant is not necessarily accompanied by intolerance to another antidepressant, even within the same drug class 16 ; therefore, patients who respond poorly to one drug or who experience adverse effects may benefit Context Although current depression treatment guidelines recommend continuing antidepressant therapy for at least 4 to 9 months, many patients discontinue treatment prematurely, within 3 months. Objectives To investigate the relationship between patient-physician communication and the continuation of treatment with antidepressants and to explore the demographics, adverse effects, therapeutic response, and frequency of follow-up visits. Design, Setting, and Patients A total of 401 telephone interviews of depressed patients being treated with selective serotonin reuptake inhibitor (SSRI) therapy between December 15, 1999, and May 31, 2000, were conducted and 137 prescribing physicians completed written surveys from rthern California Kaiser Permanente health maintenance organization outpatient clinics. Main Outcome Measures Patient-physician communication about therapy duration and about adverse effects; therapy discontinuation or medication switching within 3 months after start of SSRI therapy. Results Ninety-nine physicians (72%) reported that they usually ask patients to continue using antidepressants for at least 6 months, but 137 patients (34%) reported that their physicians asked them to continue using antidepressants for this duration and 228 (56%) reported receiving no instructions. Patients who said they were told to take their medication for less than 6 months were 3 times more likely to discontinue therapy (odds ratio [OR], 3.12; 95% confidence interval [CI], 1.21-8.07) compared with patients who said they were told to continue therapy longer. Patients who discussed adverse effects with their physicians were less likely to discontinue therapy than patients who did not discuss them (OR, 0.49; 95% CI, 0.25-0.95). Patients who reported discussing adverse effects with their physicians were more likely to switch medications (OR, 5.60; 95% CI, 2.31-13.60). Fewer than 3 follow-up visits for depression, adverse effects, and lack of therapeutic response to medication were also associated with patients discontinuing therapy. Conclusions Discrepancies exist between instructions that physicians report they communicate to patients and what patients remember being told. Explicit instructions about expected duration of therapy and discussions about medication adverse effects throughout treatment may reduce discontinuation of SSRI use. Our finding that patients with 3 or more follow-up visits were more likely to continue using the initially prescribed antidepressant medication suggests that frequent patient-physician contact may increase the probability that patients will continue therapy. JAMA. 2002;288:1403-1409 www.jama.com Author Affiliations: Division of Research, Kaiser Permanente Medical Care Program, Oakland, Calif (Drs Bull and Lee, Ms Hunkeler, and Mr Fireman), and Outcomes Research and Management Department, Merck & Co Inc, West Point, Pa (Drs Hu, Ming, and Markson). The research was completed while Dr Bull was working at the Kaiser Permanente Division of Research. He is currently with Alza Pharmaceuticals, Mountain View, Calif. Financial Disclosure: Drs Hu, Ming, and Markson are employees at Merck & Co Inc, and own stock and/or hold options in the company. Corresponding Author and Reprints: Scott A. Bull, PharmD, c/o Enid M. Hunkeler, MA, Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612-2304 (e-mail: scott.bull@alza.com). The Patient-Physician Relationship Section Editor: Richard M. Glass, MD, Deputy Editor. 2002 American Medical Association. All rights reserved. (Reprinted) JAMA, September 18, 2002 Vol 288,. 11 1403

from having their initial antidepressant medication switched. 1 This switching requires good communication between patients and clinicians about treatment experiences. Good communication has been shown to improve patient adherence to treatment instructions, especially in treatment for such chronic conditions as hypertension. 17-19 With bettertolerated medications available, nonadherence to medication regimens may result from poor patient commitment to treatment rather than from medication adverse effects. 20 In addition, for depression care, both depressive symptoms and the attached social stigma present challenges to good patientphysician communication. To date, research on patient-physician communication in depression care is limited. Available data suggest that explicit communication with patients regarding the expected duration of antidepressant therapy may reduce premature discontinuation of medication use. 11 We hypothesized that better communication between patients and physicians about antidepressant treatment, both before and during treatment, may promote favorable patterns of medication use. Fewer patients may prematurely discontinue treatment; more patients may have their medications switched because of adverse effects or poor treatment response. We conducted surveys of patients who recently began taking a selective serotonin reuptake inhibitor (SSRI) for treatment of a new or recurrent episode of depression and surveys of their prescribing physicians. We investigated the relationship between patient-physician communication about antidepressant therapy and discontinuation of use and switching of antidepressants. METHODS Patient Information The study was conducted at the rthern California Kaiser Permanente Medical Care Program, which serves 3 million members at 16 hospitals and 31 outpatient clinics. Health plan databases were used to identify potential study participants who received an SSRI for new or recurrent depression between December 15, 1999, and May 31, 2000. Patients were eligible for inclusion if they had recently begun taking an SSRI antidepressant (at least 6 months since any previous antidepressant) and were diagnosed as having major depression or depressive disorder (International Classification of Diseases, Ninth Revision, code 296.2 or 311) within 30 days before or after the date the medication was dispensed; were from 18 to 75 years old; and had no concurrent comorbidity of bipolar disorder, bulimia, eating disorder, dementia, chemical dependency, or psychotic disorder and did not have the diagnosis of cancer, acute myocardial infarction, or stroke recorded in the health plan s databases. Fluoxetine hydrochloride or paroxetine was prescribed for 94% of study patients. Prescribing physicians were asked permission to invite their patients to participate. Invitation letters were sent to patients on behalf of their physicians. The letter outlined the study objectives and informed patients that they would be telephoned and asked to be interviewed. A stamped, self-addressed postcard was enclosed for return within 7 days if the patient did not wish to participate. The study protocol was approved by the rthern California Kaiser Permanente Institutional Review Board. The patient questionnaire was divided into 3 parts. Nearly all patients were interviewed within 75 to 105 days after the start of antidepressant therapy. In part 1, patients confirmed that they had begun taking the antidepressant prescribed to them. To identify continuers, discontinuers, and switchers, patients were asked whether they were still taking the SSRI antidepressant initially prescribed and, if not, whether they were taking a different antidepressant. Patients were also asked what their physician told them before initiating treatment. Questions included, Howlongwereyoutoldtostay on the antidepressant prescribed? and How long were you told that it would take for the [index SSRI] to begin working? Patients were also asked whether their physician had discussed potential adverse effects with them before and during treatment. In part 2, patients reported whether they had experienced any of 17 adverse effects associated with SSRIs. For each adverse effect experienced, patients were asked to rate on a 4-point scale how bothersome it had been to them (1, not bothersome at all ; 2, somewhat bothersome ;3, a lot bothersome ;4, extremely bothersome ). In part 3, patients rated on a 5-point scale changes in their depressive symptoms since starting treatment (1, much better ;2, somewhat better ;3, about the same ; 4, somewhat worse ; 5, much worse ). Patients also completed the 7-item Beck Depression Inventory Fast Screen (BDI-FS) 21 about the severity of their depression. The patient questionnaire was pilot-tested with 22 depressed patients. The interview lasted 15 to 25 minutes. Physician Survey The prescribing physicians completed a written questionnaire about what they usually communicated to their patients about depression treatment. Two questions were used to assess how information communicated by physicians affected patients treatment expectations: How long do you usually tell your patients they will be taking the antidepressant? and How long do you usually tell your patients that it will take for the antidepressant to begin working? Physicians not responding to the initial mailed questionnaire within 2 weeks were e-mailed an electronic copy of the survey and given a follow-up telephone call to solicit a response. The physician survey was pilot-tested with 6 psychiatrists and 6 primary care physicians. Statistical Analysis To examine the association of patientphysician communication with antidepressant drug use, 2 logistic regression models were specified. The first compared patients who reported discontinuing use of the initial antidepressant with patients who at the interview reported that they were still continuing to take the initial antidepressant. The second 1404 JAMA, September 18, 2002 Vol 288,. 11 (Reprinted) 2002 American Medical Association. All rights reserved.

compared patients who reported that they had switched antidepressants with patients who reported that they were still taking the antidepressant initially prescribed. We characterized variables selected for the model as communication variables, adverse effect experiences, and clinical factors. Communication Variables Separate variables were created for patients who reported discussing adverse effects with their physician before treatment and during treatment. Other communication variables that could also influence medication treatment patterns were tested in the models: reporting being told to take the antidepressant for at least 6 months and reporting being told that the medication would require 4 or more weeks to take effect. Six months was selected because it represented the minimum duration of treatment required to complete the short-term recovery and continuation phase. 1 Experiences With Adverse Effects To examine the impact of adverse effects on patients continuing their initial therapy, indicators were created for patients who reported more than 1 adverse effect (a lot or extremely bothersome). We also examined the relation between number of adverse effects experienced ( 3) and frequency of discontinuing use of or switching the medication. Clinical Variables Clinical variables included the BDI-FS assessment of depression severity (minimal, mild, moderate, or severe) at the patient interview, degree to which global depression symptoms improved (dichotomized as at least somewhat better vs about the same or worse ) since start of medication use, and participation in a behavioral or counseling intervention. The number of depression-related follow-up visits with a physician (dichotomized at 3) came from the health plan s databases. To control for potential confounding factors, the models included patient s age, sex, race, educational level, previous use of antidepressants, and specialty of treating physician (psychiatrists or other specialty). A stepwise procedure was used to construct the final models. Variables significantly related to outcomes at the P.05 level were included. RESULTS Physicians gave permission to contact 765 of the 1050 potentially eligible study participants. Of the 765, 33% of 260 patients were excluded as follows: 40 of those (15%) never started taking the medication, 36 (14%) took an antidepressant within 6 months before the index date, 17 (7%) did not speak English, 97 (37%) could not be reached by telephone within 4 months of starting treatment (with at least 3 attempts), and 31 (12%) did not respond to the survey for reasons such as inability to concentrate. Eligibility could not be determined for 39 (15%) of the patients contacted. Of the remaining 505 eligible patients, 401 (79%) completed the telephone survey. On average, participants were somewhat younger (mean age 45.8 vs 49.8 years) and more likely to be women (71% vs 62%) than nonparticipants. Of the 167 physicians who treated study participants, 137 (82%) returned the questionnaire. Among them, 15 (11%) were family practice physicians, 75 (55%) were internal medicine physicians, 45 (33%) were psychiatrists, and 2 (1%) had no specialty named. significant differences were detected between psychiatrists and nonpsychiatrists with respect to information communicated to patients about duration of therapy and time before the medication took effect. Therefore, we grouped both psychiatrists and nonpsychiatrists together in all analyses. The mean age of study participants was 45.8 years. Two hundred sixtyseven (67%) of the participants were non-hispanic white and 284 (71%) were women. statistically significant differences in demographic characteristics were found between patients who continued, discontinued, or switched medication use (TABLE 1). One hundred fifty-one patients (38%) reported that they had previously taken antidepressants but not within 6 months before study entry. Of the 401 patients, 133 (33%) reported that they were no longer taking the original antidepressant: 54 (13%) had switched to a different antidepressant, and 79 (20%) had discontinued antidepressant treatment. Of those not taking the original antidepressant, 93 (70%) stopped using the medication without consulting their physicians (14 [15%] of whom were subsequently prescribed a different antidepressant), most often due to adverse effects 33 (36%), followed by 22 (24%) feeling better, 19 (20%) for lack of efficacy, and 19 (20%) for other reasons. Seventy-two percent of 137 physicians reported that they usually told patients to take the medication for at least 6 months; only 29 (21%) reported that they initially do not specify treatment duration (ie, that they do not tell patients precisely how long to take the medication, but they would rather wait to see how they feel). In contrast, 137 patients (34%) reported that they were told by their prescribing physician to take the antidepressants for at least 6 months, and 228 (56%) reported receiving no instructions about expected therapy duration. Nevertheless, an association was found between what patients reported that they were told and what their treating physicians indicated they usually tell their patients. For example, patients whose physicians usually tell their patients to take antidepressants for at least 6 to 11 months reported their mean treatment duration was 6.8 months, but patients whose physicians usually tell their patients to continue antidepressant therapy for 3 to 5 months reported their mean treatment duration was 3.0 months. We observed a similar modest correlation between patients expectations about how long it would take for the medication to begin working and their physicians reports about when to expect it to take effect (r=0.11; P=.07). TABLE 2 shows the number and percentage of patients who described aspects of patient-physician communica- 2002 American Medical Association. All rights reserved. (Reprinted) JAMA, September 18, 2002 Vol 288,. 11 1405

tion, medication adverse effects, and clinical variables grouped by antidepressant use status. Thirty-six patients (9%) reported that they were told to take medication for less than 6 months, and 192 (48%) reported that they were told by a physician or pharmacist about medication adverse effects. Two hundred eight participants (52%) reported experiencing 3 or more adverse effects, and 219 (55%) reported 1 or more adverse effect that was either a lot or extremely bothersome. Patients who reported that they were told to take their medication for less than 6 months had 3.12 times higher odds of discontinuing antidepressant therapy than patients who reported they were told to take the medication for 6 or more months (TABLE 3). Communication about adverse effects significantly decreased the odds of discontinuing antidepressant therapy, as did visiting a physician 3 or more times after starting a medication regimen and rating depression symptoms as improved. Presence of adverse effects (a lot or extremely bothersome) significantly increased the odds of discontinuing medication use. Patients who were separated, divorced, or widowed were more likely to discontinue antidepressant treatment than patients who were currently married. Switching medications was significantly associated with presence of adverse effects and discussing adverse effects at both the start of therapy and follow-up (TABLE 4). Patients who continued to have severe symptoms were 6 times more likely to switch medications. Table 1. Characteristics of Patients in Study Population, by Treatment Status 3 Months After Initiating Therapy* Characteristics. (%) of Patients Receiving SSRI Therapy Discontinued (n = 79) Switched (n = 54) Continued (n = 268) All Patients (n = 401) Age, mean (SD), y 44.5 (16) 45.4 (13) 46.3 (16) 45.8 (15) Women 52 (66) 39 (72) 193 (72) 284 (71) Race White, non-hispanic 43 (54) 42 (78) 182 (68) 267 (67) Black 9 (11) 4 (7) 23 (9) 36 (9) Latino or Hispanic 15 (19) 1 (2) 26 (10) 42 (10) Asian 3 (4) 3 (6) 9 (3) 15 (4) Other race 9 (11) 4 (7) 28 (10) 41 (10) Marital status Married 34 (43) 27 (50) 154 (57) 215 (54) Never married 14 (17) 10 (18) 40 (15) 64 (16) Separated, divorced, or widowed 31 (39) 16 (30) 72 (27) 119 (30) Did not know or refused to state 0 (0) 1 (2) 2 ( 1) 3 ( 1) Education High school 28 (35) 15 (28) 73 (27) 116 (29) Some college 31 (39) 23 (43) 100 (37) 154 (38) College or graduate 20 (25) 16 (30) 94 (35) 130 (32) Don t know/refused to state 0 (0) 0 (0.0) 1 ( 1) 1 ( 1) Employment status Employed 48 (61) 37 (68) 164 (61) 249 (62) Unemployed 10 (13) 8 (15) 2 (8) 39 (10) Homemaker 7 (9) 3 (6) 29 (11) 39 (10) Retired 11 (14) 4 (7) 41 (15) 56 (14) Did not know or refused to state 3 (4) 2 (4) 13 (5) 18 (4) * statistical difference is present for discontinued vs continued and switched vs continued on any of these characteristics. Percentages may not sum to 100 due to rounding. SSRI indicates selective serotonin reuptake inhibitor. COMMENT Successful antidepressant treatment requires patients to continue therapy long enough to provide some benefit and to reduce the likelihood of relapse. 1-3 Our findings show that premature discontinuation depends on multiple factors, including patient-physician communication, family support, clinical response to therapy, and adverse effects. Although explicit communication increased the likelihood of continuing treatment, there appeared to be a communication gap between patients and treating physicians. Whereas 72% of physicians said they usually tell patients to continue using antidepressants for at least 6 months, only 34% of patients reported being told that. Furthermore, more than half of patients reported not being told about expected therapy duration. Patients failure to remember specific information communicated to them by their physicians may partially explain the gap. If so, we suggest that it may be helpful for physicians to reinforce expected duration of treatment to their patients during follow-up visits. Discussing adverse effects with patients during treatment was associated with less premature discontinuation. This outcome may have resulted from patients receiving information and support from their physicians when adverse effects occurred. Informing patients in advance about adverse effects has been reported to prevent patients from fearing adverse effects and to increase patients physiologic tolerance to antidepressants. 22 We suggest that physicians discuss adverse effects with patients throughout treatment to encourage their continuation of antidepressant therapy. We also found that switching medication was related to discussions about adverse effects before and during treatment. Switching medications as a result of these discussions can be considered a favorable outcome if use of a different medication is associated with greater treatment continuation and improved symptoms. Both the number of adverse effects and their perceived bothersomeness indicate the importance of patientphysician discussions about medication adverse effects. The findings that 55% of patients experienced 1 or more adverse effects (a lot or extremely bothersome) and 29% of patients had 1 or more extremely bothersome adverse effects should lead physicians to expect that at least half their patients receiv- 1406 JAMA, September 18, 2002 Vol 288,. 11 (Reprinted) 2002 American Medical Association. All rights reserved.

ing SSRIs will experience potentially troublesome adverse effects. Physicians should therefore discuss adverse effects with patients during treatment. Physicians who seek to mitigate patients concerns by only selectively warning them of adverse effects may need to reconsider this practice. The findings indicate that frequent office visits after start of pharmacotherapy are associated with continuation of initial antidepressant treatment. This finding supports the new Health Plan Employer Data and Information Set measure for antidepressant manage- Table 2. Antidepressant Treatment Status 3 Months After Start of Treatment in Relation to Patient-Physician Communication, Medication Adverse Effects, and Clinical Improvement* Factors Discontinued (n = 79). (%) of Patients Receiving Serotonin Reuptake Inhibitors Switched (n = 54) Continued (n = 268) All Patients (n = 401) Discontinued vs Continued P Values Switched vs Continued Communication factors reported by patients Told how long to continue with medication at start of therapy? 6 mo 15 (19) 4 (7) 17 (6) 36 (9) 6 mo 17 (21) 24 (44) 96 (36) 137 (34).001.42 Duration not specified 47 (59) 26 (48) 155 (58) 228 (56) Told how long it would take for medication to begin working at start of therapy? 4 wk 14 (18) 10 (18) 50 (19) 74 (18) 4 wk 48 (61) 36 (67) 173 (65) 257 (64).63.93 Duration not specified 17 (21) 8 (15) 45 (17) 70 (17) Told about adverse effects by pharmacists or physicians at start of therapy? Yes 41 (52) 35 (65) 113 (42) 189 (47) 38 (48) 19 (35) 155 (58) 212 (53).13.002 Discussed adverse effects with physician or pharmacist during treatment? Yes 21 (27) 45 (83) 126 (47) 192 (48) 43 (54) 8 (15) 111 (41) 162 (40).004.001 adverse effect experienced 15 (19) 1 (2) 31 (12) 47 (12) Adverse effects Experienced 1 extremely bothersome adverse effect? 54 (68) 25 (46) 206 (77) 285 (71) Yes 25 (32) 29 (54) 62 (23) 116 (29).13.001 Experienced 1 moderately or extremely bothersome adverse effect? 33 (42) 9 (17) 140 (52) 182 (45) Yes 46 (58) 45 (83) 128 (48) 219 (55).10.001 Experienced adverse effects 3 39 (49) 16 (30) 138 (51) 193 (48) 3 40 (51) 38 (70) 130 (48) 208 (52).74.003 Clinical factors Results of BDI-FS at 3 months after starting therapy Minimal (0-3) 45 (58) 18 (35) 165 (63) 228 (58) Mild (4-6) 17 (22) 19 (37) 48 (18) 84 (21) Moderate (7-9) 10 (13) 5 (10) 29 (11) 44 (11).83.001 Severe (10-21) 5 (6) 10 (19) 19 (7) 34 (9) Had a behavioral or counseling intervention? 50 (63) 29 (54) 130 (48) 209 (52) Yes 29 (37) 25 (46) 138 (51) 192 (48).02.49 Depression symptoms were reported improved at 3 months? 19 (24) 10 (18) 26 (10) 55 (14) Yes 60 (76) 44 (81) 242 (90) 346 (86).001.06. of depression-related office visits within 120 days after starting therapy 3 65 (82) 25 (46) 170 (63) 260 (65) 3 14 (18) 29 (54) 98 (37) 141 (35).002.02 *BDI-FS indicates Beck Depression Inventory Fast Screen. Percentages may not sum to 100 due to rounding. The numbers do not add up to their respective totals due to missing data. 2002 American Medical Association. All rights reserved. (Reprinted) JAMA, September 18, 2002 Vol 288,. 11 1407

Table 3. Factors Associated With Discontinuing Use of the Initial Antidepressant Medication Within 3 Months of Starting Treatment: Results of Multivariate Model* Variable Communication factors reported by patients Told how long to continue with medication? 6 mo Odds Ratio (95% Confidence Interval) 6 mo 3.12 (1.21-8.07) Duration not specified 1.02 (0.52-2.00) Discussed adverse effects with physician during treatment? Yes 0.49 (0.25-0.95) adverse effect experienced 1.82 (0.78-4.24) Adverse effects Experienced 1 moderately or extremely bothersome adverse effect? Yes 2.94 (1.51-5.71) Clinical factors Depression symptoms were reported improved at 3 months? Yes 0.40 (0.20-0.82) Had 3 office visits within 3 months? Yes 0.40 (0.19-0.82) Marital status Married Never married 1.74 (0.80-3.76) Separated, divorced, or widowed 2.83 (1.49-5.39) *Odds ratio and 95% confidence intervals compare the 79 patients who discontinued therapy with the 268 who continued it. Table 4. Factors Associated With Switching the Initial Antidepressant Medication Within 3 Months of Starting Treatment: Results of Multivariate Model* Odds Ratio Variable (95% Confidence Interval) Communication factors reported by patients Told about potential adverse effects before starting treatment? Yes 3.02 (1.52-6.02) Discussed adverse effects with physician during treatment? Yes 5.60 (2.31-13.60) adverse effect experienced 0.75 (0.08-7.15) Adverse effects Experienced 1 moderately or extremely bothersome adverse effect? Yes 3.09 (1.30-7.31) Clinical factors Results of BDI-FS at 3 months after starting therapy Minimal (0-3) Mild (4-6) 4.21 (1.81-9.78) Moderate (7-9) 1.39 (0.44-4.39) Severe (10-21) 6.15 (2.11-17.89) Had a behavioral or counseling intervention? Yes 0.42 (0.21-0.87) *BDI-FS indicates Beck Depression Inventory Fast Screen. Medication switching was reduced with concurrent use of a behavioral or counseling intervention. Odds ratios and 95% confidence intervals compare the 54 patients who switched with 268 who continued therapy. ment developed by the National Committee for Quality Assurance as one of the accreditation criteria for managed care organizations. This measure requires antidepressant management to include at least 3 follow-up contacts during the first 12 weeks of treatment. 23 Our study results also showed a correlation between clinical response to medication and patterns of SSRI medication use. This correlation is consistent with an early study showing that depression itself is a risk factor for nonadherence to medical treatment. 24 In our study, patients who remained severely depressed, according to the BDI-FS (applied during the telephone survey), were 6 times more likely to switch to a different medication. We believe that this outcome is positive and indicates that physicians were aware of nonresponse to the treatment regimen selected initially. Close follow-up of these patients is warranted to ensure that they are offered other therapy if appropriate. When initially prescribing antidepressants, physicians should also consider the greater likelihood of treatment discontinuation in some populations. We found that separated, divorced, and widowed patients were more than twice as likely to discontinue antidepressant use as married patients. Social support may encourage them to continue treatment. The study captures information communicated about antidepressant treatment from the perspective of both the physician and the patient. The study provides information from participants about their perception of treatment experiences during routine care (ie, not as part of a clinical study protocol). Rates of discontinuation (20%) observed in our study were comparable with rates typically seen throughout the Kaiser Permanente rthern California Region (J. Chan, PharmD, PhD, unpublished data, 1999) but are higher than rates typically seen in randomized controlled clinical trials of SSRIs. 14 Higher rates of treatment discontinuation and switching observed in the naturalistic setting are probably due to both differences in the populations studied and intensity of follow-up care provided to patients. 1408 JAMA, September 18, 2002 Vol 288,. 11 (Reprinted) 2002 American Medical Association. All rights reserved.

A limitation of this study is that the data from the physicians did not refer to specific patients but to the usual information physicians routinely communicated to patients. Asking physicians to review the records of each patient and to report what they told that patient months ago would have been impractical, and, furthermore, such information may not routinely be recorded in medical records. This lack of patient-specific information probably makes it more difficult to establish an association between patient-physician responses. However, our data still demonstrated a modest correlation between physicians and their patients expectations of duration of treatment and interval before treatment response. Because patient participation in the study was voluntary and our study patients may be more cooperative than the usual patient population, our findings may overestimate the proportion of patients who communicate well with their physicians. In addition, participants may be more likely to provide socially desirable responses, which could conceal a portion of actual communication observed in this study (eg, if a patient discontinued using medication without consulting his/her physician). To minimize this potential bias, we obtained information on frequency of physician office visits from the health plan computerized registration database rather than patients self-report. We also assured participants that their responses would be anonymous and would not be passed on to their treating physician. Some questions asked patients to report information communicated to them for up to as long as 3 1 2 months before the telephone interview. Memory failure, variation in response to treatment, or both may have contributed to the discrepancy observed between physician and patient responses. In addition, the status of medication use at the time of the survey may have influenced what patients reported being told about treatment. For example, patients who switched or discontinued using the originally prescribed SSRI may have been more likely to report certain aspects of information communicated to them. However, querying patients on a more frequent basis to minimize this potential bias may have yielded an elevated adverse effect rate and may have produced the unintended effect of enticing participants to ask particular or more frequent questions than usual of their treating physician. Despite these limitations, we believe that our findings are valid for the population studied and have major implications for depression care. Conclusions Discrepancies exist between instructions that physicians report they communicate to patients and what patients remember being told. Explicit instructions about expected duration of therapy and discussions about medication adverse effects throughout treatment may reduce discontinuation of SSRI use. Our finding that patients with 3 or more follow-up visits were more likely to continue taking the initially prescribed antidepressant medication suggests that frequent patient-physician contact may increase the probability that patients will continue therapy. Author Contributions: Kaiser Permanente investigators were fully responsible for patient identification, data collection, data coding, quality assurance, and statistical analysis. Merck & Co had no access to patient and physician data. Dr Bull, the principal investigator, had full access to the data, wrote the first draft of the manuscript and revision in response to the reviewers comments, and takes full responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Bull, Hu, Hunkeler, Markson, Fireman. Acquisition of data: Bull, Hunkeler, Lee, Fireman. Analysis and interpretation of data: Bull, Hu, Hunkeler, Lee, Ming, Markson, Fireman. Drafting of the manuscript: Bull, Hunkeler. Critical revision of the manuscript for important intellectual content: Bull, Hu, Hunkeler, Lee, Ming, Markson, Fireman. Statistical expertise: Hu, Lee, Ming, Markson, Fireman. Obtained funding: Bull, Hunkeler. Administrative, technical, or material support: Bull, Hunkeler, Lee. Funding/Support: The research was supported by a grant from Merck & Co Inc, West Point, Pa. Acknowledgment: We thank Diane F. Galligan, AA, CCHT, the Kaiser Permanente Division of Research, Oakland, Calif, for coordinating patient and physician recruitment and for conducting surveys with study participants. The Kaiser Permanente Medical Editing Department provided editorial assistance. REFERENCES 1. Depression Guideline Panel. Depression in Primary Care, Vol. 2: Treatment of Major Depression. Rockville, Md: US Dept of Health and Human Services, Public Health Service, and Agency for Health Care Policy and Research; 1993. Clinical Practice Guideline. 5. 2. Schulberg HC, Katon W, Simon GE, Rush AJ. Treating major depression in primary care practice. Arch Gen Psychiatry. 1998;55:1121-1127. 3. American Psychiatric Association, Work Group on Major Depressive Disorder. Practice guideline for the treatment of patients with major depression [Web site]. Available at: http://www.psych.org/clin_res /Depression2e.book.cfm. Accessed August 22, 2001. 4. Johnson DA. Depression: treatment compliance in general practice. Acta Psychiatr Scand Suppl. 1981; 290:447-453. 5. Frank E, Prien RF, Kupfer DJ, Alberts L. Implications of non-compliance on research in affective disorders. Psychopharmacol Bull. 1985;21:37-42. 6. Myers ED, Branthwaite A. Out-patient compliance with antidepressant medication. Br J Psychiatry. 1992;160:83-86. 7. Simon GE, von Korff M, Wagner EH, Barlow W. Patterns of antidepressant use in community practice. Gen Hosp Psychiatry. 1993;15:399-408. 8. Venturini F, Sung JC, Nichol MB, Sellner JC. Utilization patterns of antidepressant medications in a patient population served by a primary care medical group. J Managed Care Pharm. 1999;5:243-249. 9. Melfi CA, Chawla AJ, Croghan TW, Hanna MP, Kennedy S, Sredl K. The effects of adherence to antidepressant treatment guidelines on relapse and recurrence of depression. Arch Gen Psychiatry. 1998; 55:1128-1132. 10. Katon W, von Korff M, Lin E, Bush T, Ormel J. Adequacy and duration of antidepressant treatment in primary care. Med Care. 1992;30:67-76. 11. Lin EH, von Korff M, Katon W, et al. The role of the primary care physician in patients adherence to antidepressant therapy. Med Care. 1995;33:67-74. 12. Katon W, von Korff M, Lin E, et al. Collaborative management to achieve treatment guidelines. JAMA. 1995;273:1026-1031. 13. Katon W, Robinson P, von Korff M, et al. A multifaceted intervention to improve treatment of depression in primary care. Arch Gen Psychiatry. 1996; 53:924-932. 14. Hotopf M, Hardy R, Lewis G. Discontinuation rates of SSRIs and tricyclic antidepressants. Br J Psychiatry. 1997;170:120-127. 15. Linden M, Gothe H, Dittmann RW, Schaaf B. Early termination of antidepressant drug treatment. J Clin Psychopharmacol. 2000;20:523-530. 16. Brown WA, Harrison W. Are patients who are intolerant to one serotonin selective reuptake inhibitor intolerant to another? J Clin Psychiatry. 1995;56:30-34. 17. Svensson S, Kjellgren KI, Ahlner J, Saljo R. Reasons for adherence with antihypertensive medication. Int J Cardiol. 2000;76:157-163. 18. Sarrel PM. Improving adherence to hormone replacement therapy with effective patient-physician communication. Am J Obstet Gynecol. 1999;180(3 pt 2):S337-S340. 19. Miller NH. Compliance with treatment regimens in chronic asymptomatic disease. Am J Med. 1997; 102(2A):43-49. 20. Urquhart J. New insight into patient noncompliance with prescribed drug regimens. Clin Res. 2001; 1:26-32. 21. Beck AT, Steer RA, Brown GK. BDI: FastScreen for Medical Patients. Marrickville, Australia: Psychological Corp; 2001. 22. Blackwell B. Antidepressant drugs. J Clin Psychiatry. 1982;43(11 pt 2):14-21. 23. National Committee for Quality Assurance. HE- DIS 2000: Technical Specifications. Vol 2. Washington, DC: National Committee for Quality Assurance; 1999:105-110. 24. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment. Arch Intern Med. 2000;160:2101-2107. 2002 American Medical Association. All rights reserved. (Reprinted) JAMA, September 18, 2002 Vol 288,. 11 1409