Eugene H. Makela

Multiple Antipsychotic Medication Prescribing Patterns

OBJECTIVE: To assess current prescribing practices regarding concomitant use of antipsychotic medications and summarize the reasons clinicians may prescribe >1 scheduled agent. METHODS: The pharmacy identified patients at William R Sharpe Jr Hospital currently receiving antipsychotic therapy. All patients receiving ≥2 scheduled antipsychotic agents concomitantly were included in the study. Data regarding the demographics, current medication combinations used, history of therapeutic regimens tried, and prescriber rationale were prospectively evaluated for a 60-day period beginning December 13, 2000, and ending February 10, 2001. Prescriber rationale for using >1 antipsychotic simultaneously and other drug therapy regimens that had been tried were compared with chart documentation and published therapeutic guidelines for schizophrenia. RESULTS: Over a 60-day surveillance period, 206 patients were placed on scheduled antipsychotic medications, with 85 (41%) receiving at least 2 agents. Responders to a prescriber questionnaire (59%) indicated the most common rationale for combination therapy was augmentation; the least likely rationale was cross-titration. Survey responses also indicated a belief that there was questionable therapeutic benefit in more than half of the patients being treated with multiple antipsychotic combinations. Additionally, chart documentation showed that the majority of these patients did not receive an adequate trial of monotherapy with other atypical or typical agents, or clozapine prior to the combination antipsychotic regimen. Fifty-one percent of medical records did not document the rationale for concomitant therapy. CONCLUSIONS: Due to the lack of published data, the practice of using multiple antipsychotic agents is considered to be a gray area that requires the prescriber to be at a heightened level of awareness in assessing effectiveness and safety. Documentation of rationale, adverse effects, and response to the treatment regimen is essential in providing optimal care for the patient.

On the nature of Wisconsin Card Sorting Test performance in schizophrenia

Performance on the Wisconsin Card Sorting Test (WCST) is widely reported to be impaired in patients with schizophrenia. It has been hypothesized that the performance deficit on the WCST in schizophrenia is related to a dysfunction of the frontal lobe, specifically the dorsolateral prefrontal cortex. This hypothesis was tested by comparing a group of patients with schizophrenia to patients with low grade right or left frontal lobe tumors and a group of patients with non-frontal high grade tumors. The results demonstrated a remarkable similarity in performance on the WCST between patients with schizophrenia and patients with right frontal lobe tumors. Patients with left frontal lobe tumors, non-frontal tumors, and normal control subjects did not show the same pattern of performance. This study provides support for frontal lobe dysfunction in the symptomatology of schizophrenia.

Depression in Patients with Type 2 Diabetes: Impact on Adherence to Oral Hypoglycemic Agents

Background: Adherence to oral hypoglycemic agents (OHAs) is important for adequate glycemic control and prevention of future complications in patients with type 2 diabetes. Objective: To examine the impact of depression on adherence to OHAs in patients newly diagnosed with type 2 diabetes. Methods: Patients newly diagnosed with type 2 diabetes during a 4 year period were identified from a Medicaid claims database. Presence of preexisting depression was determined on the basis of ICD-9-CM codes. Adherence to OHAs was computed using prescription refill data for a 12 month follow-up period from the date of the index OHA prescription. Two separate adherence indices (Medication Possession Ratio-1 [MPR-1], Medication Possession Ratio-2 [MPR-2]) were computed. The impact of depression on adherence was assessed after controlling for confounders such as demographics, comorbidity, provider interaction, complexity of regimen, and diabetes severity. Results: A total of 1326 newly diagnosed patients with type 2 diabetes were identified (depressed = 471; nondepressed = 855). Results of the study indicated that patients with depression had significantly lower adherence (MPR-1 86%; MPR-2 66%) to OHAs compared with patients without depression (MPR-1 89%; MPR-2 73%). Multivariate results indicated that depression was a significant predictor of adherence, with depressed patients being 3–6% less adherent to OHAs than nondepressed patients, after controlling for confounding factors. Conclusions: Depression significantly impacts adherence to OHAs in patients with type 2 diabetes. The study results imply that depression screening and treatment need to be included in the protocol for management of patients with type 2 diabetes.

Alcohol Withdrawal: What is the Benzodiazepine of Choice?:

OBJECTIVE: To review the literature concerning the use of benzodiazepines for treatment of alcohol withdrawal and to determine if the current literature assessment justifies the use of lorazepam as first-line therapy. DATA SOURCES: A thorough review of the literature was performed with an online database (BRS Colleague). Articles directed at the targeted issue were chosen and additional references were obtained from the bibliographies of these articles. STUDY SELECTION: Clinical trials and case reports concerning the use of chlordiazepoxide, diazepam, and lorazepam in alcohol withdrawal treatment were reviewed. DATA SYNTHESIS: Lorazepam is considered by many to be the drug of choice for alcohol withdrawal because it undergoes glucuronidation and has an intermediate half-life. These characteristics have suggested its superiority when treating elderly patients or patients with liver disease. However, some studies suggest that a drug with a longer half-life would provide smoother withdrawal. In addition, the number of patients with liver disease treated for alcohol withdrawal is unknown. These and other factors question the recommendation of lorazepam as the drug of choice. CONCLUSIONS: Well-controlled comparison studies should be performed before recommending the routine use of lorazepam for treating alcohol withdrawal syndrome.

Selective Serotonin-Reuptake Inhibitors in the Treatment of Premature Ejaculation

OBJECTIVE To review the use of selective serotonin-reuptake inhibitors (SSRIs) in the treatment of premature ejaculation. DATA SOURCES Articles were retrieved through a MEDLINE search (1966–January 2004). Search terms used to identify articles included serotonin uptake inhibitors, premature ejaculation, rapid ejaculation, and sexual behavior, as well as the generic names of currently available SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram. The literature search was limited to articles published in the English language containing human subjects. STUDY SELECTION AND DATA EXTRACTION Articles obtained through the literature search were evaluated, and randomized controlled trials were included in this review. Information from noncontrolled trials or case reports was considered for inclusion if it contributed to the completeness of this review and if it was the highest level of evidence available. DATA SYNTHESIS Premature ejaculation is a commonly reported sexual difficulty. Delayed ejaculation is a widely reported sexual adverse effect of SSRIs. In some men exhibiting premature ejaculation, the ability of the SSRIs to delay ejaculation has been therapeutic. Trials evaluating the ejaculation-delaying ability of SSRIs demonstrated that paroxetine, fluoxetine, sertraline, and citalopram produce a statistically significant increase in the ejaculation latency time compared with placebo. CONCLUSIONS Taking advantage of the ejaculation-delaying effects of SSRIs increases the treatment options available to prescribers and patients. Convenience and minimal adverse effect profile make these agents an alternative to previously used behavior modalities and older pharmacologic agents. Although some questions still surround the details of their use, SSRIs have the potential to improve the quality of life for men with premature ejaculation and their partners.

Comparing Adherence to and Persistence with Antipsychotic Therapy Among Patients with Bipolar Disorder

Background: Medication nonadherence is a significant problem among patients with bipolar disorder. Objective: To compare adherence and persistence among patients with bipolar disorder initiated on antipsychotics in a state Medicaid system over a 12 month follow-up period. Methods: Claims data for patients with bipolar disorder from a de-identified Medicaid database were examined. Patients were classified into 4 monotherapy treatment groups (risperidone, olanzapine, quetiapine, or typical antipsychotic) based on the first prescription filled between January 1, 1999, and December 31, 2001. Adherence and persistence were analyzed over a 12 month follow-up period. Adherence was measured using the Medication Possession Ratio (MPR). Persistence was defined as the total number of days from the initiation of treatment to therapy modification (ie, discontinuation, switching, or combination with another antipsychotic). Adjustment for confounding variables was undertaken using ordinary least-squares and Cox proportional hazard regression modeling. Results: The mean MPRs were 0.68 for risperidone (n = 231), 0.68 for olanzapine (n = 283), 0.71 for quetiapine (n = 106), and 0.46 for typical antipsychotics (n = 205). Patients initiated on typical antipsychotics were 23.6% less adherent than patients initiated on risperidone (p < 0.001). Mean persistence (days) was 194.8 for risperidone, 200.9 for olanzapine, 219.8 for quetiapine, and 179.2 for typical antipsychotics. Extended Cox regression modeling indicated no significant differences between antipsychotics in hazards of therapy modification within 250 days of initiation. However, patients initiated on typical antipsychotics were 5.2 times more likely to modify therapy compared with those initiated on risperidone after 250 days of antipsychotic therapy (p < 0.001). Conclusions: Adherence and persistence were similar between atypical antipsychotic groups. The typical antipsychotic group, however, demonstrated lower adherence and a greater likelihood of patients modifying therapy compared with the risperidone cohort

Selective serotonin reuptake inhibitor-induced akathisia

OBJECTIVE To review available information in the literature about akathisia (inner restlessness) caused by the selective serotonin reuptake inhibitors (SSRIs). DATA SOURCES Databases searched included Medline, PsychInfo, the International Pharmaceutical Abstracts, and Google Scholar. Search terms included drug-induced akathisia, psychomotor agitation, drug-induced side effect, movement disorders, and extrapyramidal symptoms. These search terms were cross-referenced with selective serotonin reuptake inhibitors and each of the currently marketed SSRIs: fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, and escitalopram. STUDY SELECTION Relevant articles were chosen if they specifically mentioned the word akathisia. Case reports were chosen based on a clear view that an SSRI was a contributing or causative agent of akathisia. DATA SYNTHESIS Recognizing akathisia is important because it can be very bothersome and may cause suicidal ideations. Akathisia can be recognized by examining symptoms, looking at predisposing factors, and using the Barnes Akathisia Rating Scale (BARS). Predisposing factors include use of multiple akathisia-inducing drugs, recent increases in SSRI dose, previous development of akathisia, baseline psychiatric disorders, and brain trauma. Treatment options include the addition of a centrally acting beta-blocker, a benzodiazepine, or an anticholinergic agent. CONCLUSION Pharmacists can play an active role in recognizing akathisia by being aware of its characteristics, conducting a thorough medication history to identify causative agents, and using BARS to evaluate patients. These efforts may preclude unnecessary discomfort for the patient and reduce the potential for nonadherence induced by akathisia.

Branded versus Generic Clozapine for Treatment of Schizophrenia

OBJECTIVE: To report clinical findings resulting from a switch from branded to generic clozapine. METHODS: Twenty patients diagnosed with schizophrenia were followed in this naturalistic outpatient study. The Positive and Negative Syndrome Scale (PANSS), Beck Anxiety Inventory (BAI), Abnormal Involuntary Movement Scale, and the Movement Disorder Assessment were used to assess differences in the clinical status of patients before and after switching from Clozaril to generic clozapine (Mylan Pharmaceuticals). Results were analyzed by means of the paired t-test and by calculation of the percent change in mean scores. A clinically significant change as measured by the PANSS was defined as a ± 20% change in mean scores at final evaluation. The design was open-label and non-blinded. RESULTS: At the final evaluation, the t-test revealed no significant differences between branded and generic clozapine for the total PA NSS, the positive symptom, negative symptom, and the general psychopathology subscales of the PANSS, and the BAI. There were no clinically significant changes for any measure. CONCLUSIONS: In this small group of patients with schizophrenia, no deterioration in clinical status in several domains was noted after changing from branded to generic clozapine. This finding is consistent with pharmacologic data suggesting bioequivalence of the 2 products. Results, however, must be interpreted cautiously due to the lack of optimal study controls and small sample size.

Medication Utilization Patterns and Methods of Suicidality in Borderline Personality Disorder

Background: Borderline personality disorder (BPD) is a psychiatric disorder characterized by suicidal thoughts/attempts and instability of mood, interpersonal relationships, and self-image. Patients with BPD engage in manipulative acts in apparent attempts to exert control in their interpersonal relationships. This issue of control may also be exhibited in their manner of self-medication. Objective: To examine the medication utilization patterns of patients with BPD versus patients without personality disorders in a control group and to compare methods of suicidality between the groups. Methods: A randomized, retrospective, chart review study was conducted at an academic medical center psychiatric hospital. The study examined the medication utilization patterns and methods of suicidality displayed over a one-year period for 29 patients hospitalized with BPD versus 29 patients in a control group. Results: The number of psychotropic, non-psychotropic, and total drugs on admission and discharge was significantly greater for patients with BPD compared with patients in the control group. There was no significant difference between the 2 groups with respect to overdose and cutting methods of suicidality. The mean number of Axis III discharge diagnoses in the control group upon discharge was significantly less than that in the study group. Approximately 25% of patients with BPD considered overdosage as a means to end their life. Conclusions: As patients with BPD receive more medications than patients without the disorder and often exhibit suicidal thoughts/attempts, clinicians should closely monitor the use of all medications.

Hypothyroidism and Depression: A Therapeutic Challenge:

OBJECTIVE: To describe a patient with longstanding depression and hypothyroidism who had marked mood improvement only after triiodothyronine (T3) was added to her thyroxine (T4) replacement therapy. CASE SUMMARY: A 50-year-old white woman had a long history of depression and documented hypothyroidism since 1991. Despite treatment with T4 with dosages up to 0.3 mg/d, she continued to be depressed, have symptoms of hypothyroidism, and have a persistently elevated thyroid-stimulating hormone concentration. Addition of a low dose of T3 to her regimen resulted in significant mood improvement. DISCUSSION: The relationship between hypothyroidism and depression is well known. It is possible that this patients long history of depression may have been a consequence of inadequately treated hypothyroidism, due either to poor patient compliance or resistance to T4. Nevertheless, her depression responded to addition of a low dose of T3 to her regimen. This case emphasizes the importance of screening depressed patients for hypothyroidism. Her clinical course also suggests that depression related to hypothyroidism may be more responsive to a regimen that includes T3 rather than to replacement with T4 alone. This is consistent with the observation that T3 is superior to T4 as adjuvant therapy in the treatment of unipolar depression. CONCLUSIONS: Depressed patients should be screened for hypothyroidism. In hypothyroid patients, depression may be more responsive to a replacement regimen that includes T3 rather than T4 alone. Therefore, inclusion of T3 in the treatment regimen may be warranted after adequate trial with T4 alone.