Dr. Peselow is research professor in the Department of Psychiatry at the New York University School of Medicine in New York City, staff psychiatrist at the Department of Veterans Affairs New York Harbor Healthcare System in New York City, and medical director at the Freedom From Fear Clinic in Staten Island, NY.

Disclosure: Dr. Peselow is on the speaker’s bureaus of Forest and Pfizer.

Acknowledgments: Dr. Peselow would like to thank Sabrina J. Khan, MD, Tara M. Pundiak, MD, Caroline Williams, MD, and Gavi Hollander, DO, for their assistance with this article.
Please direct all correspondence to: Eric D. Peselow, MD, Freedom From Fear, 308 Seaview Ave, Staten Island, NY 10305; Tel: 718-351-1717, ext 10; Fax: 718-667-8893; E-mail: ericpes@mindspring.com.

 


 

Abstract

Medication has played a major role in the alleviation of pain and suffering with respect to psychiatric treatments. At least 66% to 75% of patients who receive psychotropic drugs for various conditions have a ≥50% decrease in their symptoms and approximately 35% have a remission. To achieve this improvement, one must adhere to the therapeutic regimen. Communication between the physician and patient is paramount to achieving this adherence. There are numerous etiologies of non-compliance, including stigma and shame in needing psychiatric treatment, specific beliefs about the meaning of medication and psychiatric treatment, and the fear of psychotropic drug side effects that may be disabling and can offset the therapeutic benefit. This article assesses strategies to improve adherence with medication and other psychiatric treatments, such as psychoeducation, psychotherapy, and behavioral and social service interventions. Exploring the meaning of illness and medications—including the risk-benefit ratio of taking the medication versus the alternatives; denial; the patient’s motivation for treatment, and the patient’s expectations for treatment—are all important in improving compliance and achieving a better outcome. This article examines ways to assess non-compliance, determine the reasons for non-compliance,  and choose interventions to encourage compliance with treatment.

 

Introduction

Adherence describes a patient’s behavior in taking medication and making lifestyle changes such as following a diet or exercising as a result of the medical advice of a clinician. It has been estimated that 70% of patients do not follow simple dietary recommendations and >90% of patients who are advised to try to stop smoking do not comply.

The severity of the problem is staggering.1 A 10% to 20% non-attendance rate occurs in clinical settings for appointments made by the patient, and the rate is at least double that for those made by the clinic for the patient. Non-adherence is common in all areas of medicine for acute treatment of a medical disorder. Patients do not fill their prescriptions between 30% and 35% of the time. Patients do not complete an acute course of recommended treatment between 75% and 80% of the time. More than 25% of the time, patients with respect to psychotropics stop their medication within several days of initiating treatment. In one study, 33 of 122 patients failed to complete a 3-week course of antidepressants.2

With respect to long-term medication treatment, which is necessary for psychiatric and medical illness, more than 50% of the time patients do not comply with treatment. A study by Peselow and colleagues3 noted that only 27 of 97 patients who began prophylactic treatment following the acute resolution of antidepressant symptoms completed a 1-year maintenance trial. Another study by Khan and colleagues4 found that approximately 50% of 488 patients who received prophylactic treatment with a selective serotonin reuptake inhibitor after 6 months of stability subsequently dropped out of treatment.

Nierenberg and Kolsky5 have explored the reasons for medication non-adherence. For the patient, the meaning of taking medication determines his or her attitude in taking such medication. If the patient perceives that the medication can help, he or she will take it. Many patients have cognitive distortions concerning medication use. They often feel there is something fundamentally wrong with them if they need medication (they are “psychological misfits”). They may feel if they have to take medication, they are morally weak and the medication is simply a crutch and does not do anything for the life problems they need to deal with. Patients may also worry about the medication controlling their thoughts and actions. They may also worry about addiction to the medication. Patients are often concerned with long-term and even lifetime use.

It is important to recognize non-adherence (Table 1). Obviously, non attenders to appointments and patients who fail to achieve improvement in symptomatology must be evaluated. Non-attenders who rarely comply with any treatment regimen need to be monitored for attendance (ie, how many appointments they miss). Certainly, at each visit the clinician needs to ask the patient whether he or she is taking the medication according to the clinician’s medical advice. The clinican should acknowledge to the patient that many patients have difficulty taking their medication, explaining that there are many reasons for this. The clinician should then ask if he or she has such problems. In this manner, a patient may feel less guilty with respect to admitting non-adherence.

 

When a patient has not improved on standard appropriate regimens, the clinician should reassess the diagnosis but, more importantly, assess adherence with the treatment regimen. If the patient has been assessed, adherent consideration should be given for a change in regimen. However, if the patient has been non-adherent, the clinician should relay to the patient that he or she is short-changing himself or herself with respect to “getting better.”

Ways to improve adherence and treatment response in individuals who have distorted views of medication treatment include an explanation that the treatment can diminish the frequency and severity of symptoms (Table 2). By diminishing the frequency and severity of symptoms, the patient can meaningfully participate in therapy and more easily cope with the stressors that he or she may be experiencing. This leads to improved functioning and greater control of the patient’s life.

It is important to educate patients and their families about the need for medication and the nature of the psychiatric diagnosis. Clinicians should explain to the patient that in many cases the problem is a chemical imbalance. Although the causes of psychiatric illnesses are still being studied and the exact cause is not yet known, the aberrance in brain chemistry can be treated with psychotropic medication. Clinicians should explain to the patient that psychiatric illness should be thought of as a medical problem analogous to hypertension (where medication is used to control blood pressure) or diabetes (where medication is used to control blood sugar levels).

 

It is also important to explain that medications to treat these disorders must be taken as prescribed, usually every day on a BID or TID basis. It must also be explained to the patient that it takes a minimum of 4–6 weeks (and sometimes longer) to alleviate core target symptoms of the disorder. It should be noted that often 85% of patients after 1 week will show minimal or no change. Noting this to the patient serves to prevent discouragement. Core side effects should be explained to the patient. For example, at the outset of treatment the clinician should explain to a patient who is taking sertraline for depression that he or she may encounter agitation, irritability, gastrointestinal upset, sexual side effects, and insomnia. The patient should be informed that this occurs in 15% to 20% of instances and that the side effects can occur early on and often appear before any benefit is achieved. Often, patients show some tolerance to many side effects, and on the same dose the side effects often improve with time. However, since the somatic focus may increase in patients with anxiety and depression, they can report unusual effects often unrelated to the specific drug. It is necessary to reassure these patients. One technique that has been found useful after the patient has presented a “laundry list of side effects” is to ask them what they think is the most likely thing to happen as a result of taking the drug. When the patient admits he or she does not know but exhibits curiosity about the answer, the clinician can tell the patient that the answer is that he or she will get better. There is a 66% chance of having a >50% reduction in symptoms.

Continued frequent followup after initiation of treatment is warranted. Patients should not be given a prescription to initiate treatment and be told to come back in 1–2 months. During the initiation phase, patients should be seen every 1–2 weeks. The visit should not be a purely “psychopharmacologic management” visit where the clinician simply writes a prescription for medication. For the given psychiatric disorder, the clinician should track the symptoms that the patient complains of through defined rating scales (eg, the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression). During each visit, the severity of symptoms should be measured and improvement or worsening of symptoms between visits should be noted. The clinician should ask if the patient thinks he or she has improved from the beginning of treatment. The patient’s medication and reasons for changes in dosage should be carefully documented. The clinician should collaborate with the patient as to the speed of dose increase in order to reach an effective dose, as well as discuss when and how often the patient should take the medications.

It is important to meet early in the treatment course until the patient stabilizes. This will help enforce the importance of this course of treatment and show the clinician’s availability to help and support the patient. The clinician should expect telephone calls between sessions during which the patient will report side effects or lack of improvement. During this time, it is helpful to remind the patient that it takes time to improve, with the goal being that he or she stays with the medication and will hopefully be restored to a functional level. The clinician should try to convince the patient to stay with the treatment with the hope that the side effects will diminish with medication acclimation. Certainly, the patient should be reminded that the clinician is available by telephone. However, if the issue cannot be settled on the phone, perhaps the appointment can be moved up.

In addition to reporting symptom improvement, during each visit the clinician should track side effects. The clinician should ask the patient if he or she feels physically different from the last visit and if there are new and troubling symptoms. Clinicians should note if the patient’s side effects have become more or less troublesome as compared with the previous visit. Non-psychotropic medication, illegal substance, or alcohol use should be assessed with respect to psychotropic drug usage.

The clinician should acknowledge that continued tracking of adherence is often difficult for the patient to master, in which case the patient can use a simplified schedule (ie, QD or BID); if the patient is taking multiple drugs, it may be feasible to take these medications at the same time. These strategies may make taking medication less burdensome.

Non-adherence with psychotropics may be associated with life stressors that can worsen the underlying disease and may lead to non-adherence and non-response to medication. It is important within the “psychopharmacologic visit” to explore occupational, relational, or financial sources of stress. The goal of the visit is to help the patient locate resources that may help him or her solve such problems.

If the patient allows, the clinician should meet with the patient’s family to discuss the patient. It is important to educate the family about diagnosis, benefits and risks of psychotropic drugs, and other treatments. The involvement of a patient’s family allows the clinician to recognize factors between the parties that may be perpetuating or worsening the symptoms.

 

Specific Interventions

Mood Stabilizers for Affective Illness

It may prove beneficial to predict patients’ adherence to mood stabilizers with the intention of clinical intervention. In a seminal study by Jamison and colleagues,6 the most important reasons patients gave for non-adherence were that they did not like their moods controlled by medications, were bothered by the idea of having a chronic illness, disliked side effects (especially lethargy, decreased coordination, and dulling of the senses), missed highs, and disliked the “hassle of taking medications.” Compared to fully adherent patients, a recent study found that partially adherent subjects have significantly more resistance to prophylaxis, fear of side effects, denial of the severity of their illness, and negative attitudes toward medication in general.7 Denial of illness or lack of insight is associated with non-adherence to medication.8-10 Non-adherent patients are significantly more likely to dislike the idea of taking long-term lithium prophylaxis.7,11 Non-adherence has been associated with substance abuse10,12,13; cigarette smoking14; elevated mood15; and certain Axis II diagnoses, especially histrionic personality,12,16 although adherent patients have higher dependency scores.17 Non-adherent patients are more likely to express the need to feel in control of their lives,18 to have been diagnosed with an affective disorder for a shorter period of time,14 to have a longer length of lithium treatment,7 and to have more prior hospitalizations.12 However, patients who perceive their illness as more severe17 or have had more prior affective episodes16 are more adherent.

In a study by Stratigos and Peselow,19 non-adherent patients reported that the most common reasons for discontinuation of treatment were no longer feel ill, disliking the idea of indefinite intake, and not wanting their moods to be controlled by medications, as well as affective reasons such as missing the “highs” or feeling depressed with the hope of improving mood by stopping medication. Other researchers6,7,11,20 have found these factors in various combinations to be important in predicting non-adherence, although few if any other studies have examined the situational reasons (eg, cost, psychopharmacology set-up) for non-adherence. In the study by Stratigos and Peselow,19 11 patients (9.9%) gave cost and 11 patients (9.9%) gave issues with their primary psychopharmacology set-up (ie, 15–20-minute visits every 3–6 weeks) as their primary reason for non-adherence. Non-adherent patients also reported the stigma of mental illness as a reason for medication discontinuation. They were also significantly more likely to complain of medication side effects, be bothered by the idea of having a chronic illness, feel less attractive to others, and feel less creative. As in other studies,9,16 gender was not associated with adherence status.

Adherent patients are more likely to say that their illness is caused by biologic factors, whereas non-adherent patients are more likely to attribute their illness to life events. Few studies have investigated this, with the exception of a study by Ruscher and colleagues20 that reported that patients—many of whom had been non-adherent—blamed environmental or situational problems more than biology for causing their psychiatric illnesses. However, this study did not specifically quantify differences in attitudes between adherent and non-adherent patients. Non-adherent patients are significantly more likely to be in psychotherapy, mostly supportive therapy. This finding is rather unexpected, since one of the goals of psychotherapy with bipolar patients is to improve medication adherence,21 and other studies of psychotherapy and adherence have found a positive relationship.22,23 Fifty percent of patients consider psychotherapy “very important” in their lithium adherence.6

Psychotherapy may facilitate drug treatment by augmenting the doctor-patient relationship as well as improving attendance and drug adherence.24 To the contrary, a study of family-focused psychoeducational treatment found that participation did not predict adherence.25 Some research is available on cognitive-behavioral therapy (CBT) and adherence,22,23 but future research must examine the role of other therapies in medication adherence.

Inter-episodic subclinical, affective symptoms may be associated with adherence. Jamison and Akiskal26 theorized that these subclinical symptoms likely contribute to medication non-adherence, possibly more so than manifest symptoms, although some prior studies have found no relation.16,22,27 In the aforementioned study by Stratigos and Peselow,19 non-adherent patients manifested more inter-episodic depressive symptoms of greater severity than did adherent patients. This may explain why more non-adherent than adherent patients are in therapy. Psychosocial treatments may positively influence and provide greater prophylaxis against depressive symptoms than against mania.25,28 Manic symptoms of adherent and non-adherent patients do not differ significantly. This is contrary to an earlier study that found increased non-adherence with elevated mood.15 Thus, subclinical manic symptoms predict relapse but may not predict treatment discontinuation (G. Laje, MD, E.D. Peselow, MD, unpublished data, June 2004).

The importance of the therapeutic alliance between the physician and patient, which has a strong association with outcome in psychopharmacotherapy, cannot be understated.29 From their findings, Cochran and Gitlin30 concluded that if patients think that their psychiatrists believe in the mood stabilizer regimen and are motivated to listen, then they will have more intent to comply and more actual adherence. The therapeutic alliance must also involve the physician as a teacher. In asthma patients, another group with adherence problems, non-adherence is lower when individuals perceive receiving sufficient amounts of information and encouragement to evaluate the pros and cons of treatment, and when they are involved in decision-making at their desired level.31 A study by Seltzer and colleagues32 found that an inpatient psychoeducation program for patients with severe mental illnesses resulted in decreased patient fear of side effects or becoming addicted to their medications. (Side effects were initially the most common reason cited for medication non-adherence in this study.) In a study by Harvey and Peet,33 psychoeducational program for bipolar patients designed to increase patients’ knowledge of their medications resulted in “moderate improvement” in lithium attitudes and improved adherence. They noted that a patient can fall easily into the routine of taking their mood stabilizers without having a real understanding of their treatment. This underscores the need to provide patients with more education about their medications, not just in the acute setting but throughout treatment. In the study by Stratigos and Peselow,19 patients initially agreed to start medications based on given information and were treated long-term, but many later dropped out of treatment. Further research must investigate the most efficient and productive means to educate patients and the varying roles of patient education at different periods in the course of bipolar disorder. Frank and colleagues34 provide a more in-depth review of adherence issues.

 

Specific Issues With Antipsychotics

Numerous adherence factors are important when antipsychotics are being used to treat psychotic disorders, such as schizophrenia. Perkins35 reported that with respect to long-term treatment, at least 40% of patients stop their medication within 1 year and approximately 75% stop within 2 years. Medication side effects appear to be the main reason for non-adherence.36 Excessive sedation, anticholinergic side effects, and akathisia are thoughy to be major reasons as to why these drugs are stopped. Akathisia is particularly distressing to patients as its effects may cause aggressive and suicidal ideation. Weight gain is a major reason why many patients stop their medications, and the metabolic side effects of the atypical or second-generation antipsychotics (diabetes, hyperlipidemia) also cause discontination as well as non-adherence. Adams and Howe37 noted that hospitalized psychotic inpatients tended to focus on the secondary benefits of medication, such as keeping them out of the hospital as well as allowing them to work and maintain significant relationships. The more important these benefits were to the patient, the more likely he or she was to be adherent.

Unconscious factors are involved in medication adherence. The medication can represent a good, nurturing doctor who cares about the patient. However, it may also represent control over the patient and a violation of his or her private boundaries that may lead to self-annihilation.38 One major long-term problem was coined by Weiden and colleagues39 as an “awakening experience.” Following a patient’s first severe psychotic episode, marked improvement may occur. However, there may then be a realization by the patient that there is something wrong with him or her. This may lead to a post-psychotic depression whereby the patient may finally understand that he or she suffers from a severe and debilitating illness. The consequences of these realizations may include suicidal ideation or behavior. Such an awakening may lead to a denial and outright refusal to take antipsychotics.

Often, in order to ensure adherence with medication, psychosocial supports may be implemented. These may include supportive therapy, social skills training, and occupational therapy (which yield a lower risk of discontinuation or chance of relapse, as the patient can be observed and prodromal symptoms of relapse can be better observed). Group therapy, family therapy, and day treatment programs may also be helpful, although it is important to assess the patient’s ability to tolerate these initiatives as the patient may be too disorganized to participate.

To handle the dilemma of the patient refusing to come to outpatient treatment, some states in the United States have enacted laws enforcing mandatory treatment for the potentially violent or dangerous patient (“outpatient civil commitment”). The laws allow for a non-adherent patient to be brought in for the “involuntary” administration of depot antipsychotics.

Switching a patient to clozapine may help with adherence as he or she is forced early on to come in for weekly blood drawings for the first 6 months and biweekly blood drawings for months 7–12. This seems to improve adherence, but is sometimes conducted involuntarily. However, whether it is the superior efficacy of the drug or the fact that the patient has structured weekly or biweekly appointments, this practice may make prior non-adherent patients appreciate and become acculturated to the mental health system.

 

Specific Issues in Patients With Anxiety Disorders

The state of anxiety itself makes it hard to get patients into treatment. For example, patients with social anxiety disorder usually do not seek treatment as it is believed that the disorder is part of their “normal personality.” Only a minority of patients seek professional help. An estimated 2.4 million sufferers in the US go untreated. The nature of social anxiety disorder causes the patient to delay seeking help. When the patient does consult a doctor, it is often to seek treatment for the physical symptoms.40

Detection of obsessive-compulsive disorder (OCD) is often difficult due to patient reticence due to shame, embarrassment, denial, avoidance, and acceptance of symptoms as part of the patient’s personality. In addition, comorbidity may mask the OCD as a differential diagnosis such as depression, generalized anxiety disorder, panic disorder, or hypochondriasis, which may make the OCD seem secondary.

Panic disorder is also difficult to detect. Failure to recognize this disorder can lead to very high social and economic costs. Unexplained medical symptoms lead to over-utilization of emergency, medical, and psychiatric symptoms; they may also lead to hospitalization, which further increases cost due to excess diagnostic testing.

Psychoeducation about these disorders is important. Once a diagnosis is made, it is important to educate the patient about any misconceptions regarding treatment. For example, when it has been determined that a patient needs to be prescribed an antidepressant or benzodiazepine, the patient should be thoroughly educated about the potential side effects and goals of treatment.41 Patients will be less distressed if side effects are anticipated and more likely to be adherent if treatment goals are collaborative. In addition, patients are often comforted by the knowledge that many of the side effects will resolve within 2 weeks when tolerance develops.

Often, medication or CBT alone will not work for complete remission of an anxiety disorder. Combination treatment of pharmacotherapy is facilitative and helps with adherence. For patients with severe agoraphobia and panic, treatment often needs to be initiated with both an antidepressant and benzodiazepine (which decreases the activation the antidepressant may cause and may work to decrease the anticipatory anxiety associated with entering a phobic situation). Though reassurance by the clinician may be satisfactory, often specialized treatment may be necessary. Based upon empirical evidence, patients with panic disorder who fear bodily sensations may decrease physical sensations by utilizing breathing retraining, among other techniques. In addition, catastrophic misinterpretation of bodily sensations can be interrupted utilizing the technique of cognitive restructuring, and conditioned fear of bodily sensations can be decreased by interceptive exposure.42

Following a period of time on medication during which the panic and anticipatory anxiety is controlled, the patient may want to discontinue the medication. CBT may help the patient gain greater control and mastery over symptoms as well as fascilitate a more successful withdrawal from the medication. Intensive involvement in treatment may allow the patient to gain a greater understanding of his or her illness and may make it easier to restart treatment if necessary.

 

Conclusion

The doctor-patient relationship is perhaps the most important factor for medication adherence. When the doctor and patient have different priorities, beliefs, styles of communication, and medical expectations, adherence suffers. Adherence can be enhanced when clinicians explain to their patients the value and benefit of the proposed treatment.

The patient’s subjective feelings of distress are an important factor in adherence, as opposed to the clinician’s objective medical assessment. Patients who believe they are ill are more adherent, as they have subjective feelings that they wish to alleviate. For example, an asymptomatic patient who has hypertension is less likely to be adherent. Thus, communication between the patient and clinician is paramount. They must both specify what they want and expect from the treatment proposed. Implicit in this statement is that both the patient and the clinician can renegotiate the original “contract,” and suggestions can be made by either party to improve treatment and ensure adherence. PP

 

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