Selective Serotonin Reuptake Inhibitor/Serotonin-Norepinephrine Reuptake Inhibitor Use as a Predictor of a Diagnosis of Restless Legs Syndrome.

OBJECTIVE/BACKGROUND: Because restless legs syndrome (RLS) is a problematic syndrome, demonstrating an association between use of selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) and RLS may help direct patient care. The goals of this study were (1) to establish the incidence of RLS in mental health patients being treated with SSRIs or SNRIs in a local Veterans Affairs medical center and (2) to evaluate the frequency with which certain SSRIs or SNRIs are associated with RLS and the trend in frequency of the diagnosis since the revision of the criteria for RLS offered by the International Restless Leg Syndrome Study Group (IRLSSG), the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and the International Classification of Sleep Disorders, Revised (ICSD-3). METHODS: A retrospective chart review was used to evaluate the number of patients receiving SSRI/SNRI therapy with and without a diagnosis of RLS, with the date of the RLS diagnosis and initiation of SSRI/SNRI therapy noted. The frequency with which certain SSRIs/SNRIs were associated with RLS, and the frequency of RLS diagnoses since January 2012 were also noted. Descriptive statistics and logistic regression were used for data analysis. RESULTS: A total of 254 charts were reviewed. A majority of the patients (89.8%) were male, and 14 (5.5%) were diagnosed with RLS. A logistic regression equation approached significance in predicting RLS (P=0.053). Age and sex emerged as significant predictors of RLS. The prevalence of any individual SSRI or SNRI being associated with RLS was indeterminable. No difference was seen in the number of RLS diagnoses since the refining of the IRLSSG, DSM-5, and ICSD-3 criteria. CONCLUSIONS: The use of SSRIs/SNRIs does not seem to be associated with a diagnosis of RLS. In addition, the diagnosis of RLS does not seem to have become more common since the revision of the diagnostic criteria for the disorder.

Pediatricians' self-reported role in treating children and adolescents with major depressive disorder: a national random survey.

OBJECTIVE: Major depressive disorder (MDD) is a serious US public health problem for children and adolescents. This study explored pediatricians' self-reported role in treating children and adolescents with DSM-IV-TR MDD after the 2004 US Food and Drug Administration black-box warning. METHOD: A national random sample of pediatricians (N = 2,000) was surveyed from the beginning of November 2007 through the end of January 2008, with a usable response rate of 22.7% (408 of 1,800 deliverable surveys). Descriptive statistics and χ(2) tests were used to analyze the data on treatment versus referral of children and adolescents with MDD and on the proportion of pediatricians in 4 geographic regions who treat children and adolescents with MDD. RESULTS: The majority of the pediatricians (60.0%, 245 of 408) do not treat either children or adolescents with MDD. Fewer than one-third of the pediatricians (28.2%, 115) reported treating both children and adolescents. The majority of the pediatricians (83.6%, 341) reported referring both children and adolescents to psychiatrists for treatment. The χ(2) tests indicate that the proportion of pediatricians who treat children (P = .088) and adolescents (P = .259) does not vary significantly according to the 4 geographic regions analyzed (Northeast, South, Midwest, and West). CONCLUSIONS: On the basis of self-report, the majority of US pediatricians do not treat children and adolescents with MDD but instead refer these patients to psychiatrists. In light of the current shortage of child and adolescent psychiatrists in the United States, referral to these specialists may be problematic.

Child psychiatrists' self-reported treatment and monitoring of children and adolescents with major depressive disorder.

OBJECTIVE: Major depressive disorder (MDD) is a serious U.S. public health problem for children and adolescents. This study examined the type and course of treatment and monitoring habits of child psychiatrists treating newly diagnosed children and adolescents with MDD. Length of treatment and monitoring frequency were compared to current recommendations. METHODS: A national random sample of child psychiatrists (N = 2,250) was surveyed via a modified Dillman approach to mailed surveys. Descriptive statistics and t-tests were used to report and analyze the data. RESULTS: Of 1,982 surveys that were delivered to child psychiatrists, 316 (15.9%) were returned, with 299 surveys (15.1%) providing usable data. The child psychiatrists who responded to the survey reported that they use a combination of antidepressant and psychotherapy treatment, although many (40.1%) treat children with psychotherapy alone as a first-line treatment. With regard to pharmacotherapy for MDD, the child psychiatrists self-reported using fluoxetine or sertraline. Many child psychiatrists also use bupropion or other drug classes as a third-line treatment strategy. The child psychiatrists reported that they treat children and adolescents with antidepressant medication for an average of 10 months. This is significantly (p < 0.05) longer than the 6 month minimum recommended by the American Academy of Child and Adolescent Psychiatry (AACAP). During the first and second months of treatment, the monitoring reported was significantly (p < 0.05) less than that recommended by the U.S. Food and Drug Administration (FDA), while the reported monitoring did not differ (p = 0.10) from FDA recommendations in the third month. CONCLUSIONS: Child psychiatrists reported using combination treatment when treating children and adolescents with MDD. When they reported using antidepressant medications, the most commonly prescribed agents were fluoxetine or sertraline. Reported length of antidepressant treatment was adequate for relapse prevention. The monitoring behavior reported by respondents was not consistent with the FDA's recommendations for the first 2 months of treatment, but it was consistent for month 3.

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.

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.

Impact of depression on utilization patterns of oral hypoglycemic agents in patients newly diagnosed with type 2 diabetes mellitus: a retrospective cohort analysis.

BACKGROUND: Oral hypoglycemic agents (OHAs) are an important component in the management of type 2 diabetes mellitus (DM). Large-scale studies have demonstrated that tight glycemic control with such agents can reduce the frequency and severity of long-term DM-related complications. OBJECTIVES: The main goal of this study was to examine the impact of depression on utilization patterns of OHAs in patients newly diagnosed with type 2 DM. A secondary objective was to estimate the impact of depression on discontinuation and modification of pharmacotherapy for DM in these patients. METHODS: Patients newly diagnosed with type 2 DM during a 3-year period (1998-2000) were identified from a Medicaid claims database. Presence of preexisting depression was determined on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. The patient cohort was followed up until they received their first prescription for an OHA (1998-2001); this date was treated as the index date for the study. Utilization patterns (ie, discontinuation, augmentation, switching, non-modification) for OHAs were computed for a 12-month follow-up period after the index date. A multivariate framework was used to estimate the impact of depression on utilization patterns, controlling for confounders such as demographics, comorbidity, provider interaction, drug regimen complexity, and DM severity. RESULTS: A total of 1237 newly diagnosed type 2 DM patients were identified (depressed, n=446; nondepressed, n=791). A higher number of depressed patients (23.32%) switched or augmented therapy compared with nondepressed patients (16.18%). Also, a higher fraction of depressed patients (39.46%) discontinued OHA therapy compared with nondepressed patients (32.87%). Results of a multinomial logistic regression indicated that, controlling for covariates, patients with depression were 1.72 times more likely to switch (P=0.046) and 1.89 times more likely to augment therapy (P=0.004) compared with nondepressed patients. Logistic regression analysis also indicated that, controlling for confounding covariates, patients with depression were 1.72 times more likely to modify initial OHA therapy compared with patients without depression (P=0.003). CONCLUSION: Depression was significantly associated with utilization patterns of OHAs in these patients newly diagnosed with type 2 DM, thus possibly affecting their disease management.

The effect of depression on health care utilization and costs in patients with type 2 diabetes.

The objective of the study was to estimate the effect of depression on health care utilization and costs in patients newly diagnosed with type 2 diabetes. Patients were identified during a four-year enrollment period (1998-2001) from a Medicaid claims database. The final cohort consisted of 4,294 patients with type 2 diabetes (1,525 patients with depression; 2,769 patients without depression). Multivariate results indicated that significant utilization differences existed between the two groups: Patients who were depressed incurred a higher number of physician office visits, emergency room/inpatient admissions, and more prescriptions compared with patients who had diabetes but were not depressed. Patients with depression had nearly 65% higher overall health care costs than those without depression. Recognizing that depression is as a risk factor for increasing health care expenditures has the potential to improve diabetes management and related outcomes.

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.

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.

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.

Concomitant use of modafinil and tranylcypromine in a patient with narcolepsy: a case report.

This is a case report of a patient with narcolepsy treated simultaneously with modafinil and tranylcypromine. The concurrent use of these two medications is normally contraindicated based on theoretical concerns. To our knowledge this is the first report of the combined use of these two medications in a patient for any reason. This combination of medications was particularly effective in the treatment of the patient's narcoleptic symptoms and was well tolerated, with no evidence of the potential cardiovascular side effects. Due to modafinil's lack of sympathomimetic activity and unique pharmacological profile, it may be well tolerated with monoamine oxidase inhibitor's (MAOI's) in humans with respect to hemodynamic parameters and concerns of hypertensive crisis. Further investigation would help clarify cardiovascular safety issues in using this combined therapy. We believe that with proper informed consent from the patient and careful monitoring, a combination of an MAOI and modafinil may be a viable treatment alternative in refractory cases of narcolepsy.

SSRI-induced apathy syndrome: a clinical review.

The authors review the literature pertaining to selective serotonin reuptake inhibitor (SSRI)-induced apathy syndrome. A literature search of Medline and International Pharmaceutical Abstracts from 1970 to the present was performed for relevant articles. Twelve relevant case reports and one open-label treatment trial were identified. An amotivational, or apathy, syndrome has been reported in a number of patients receiving SSRI treatment over the last decade. This adverse effect has been noted to be dose-dependent and reversible, but is often unrecognized. This phenomenon has caused significant negative consequences for adults as well as social and academic difficulties in adolescents.

Utilizing CIWA-Ar to assess use of benzodiazepines in patients vulnerable to alcohol withdrawal syndrome.

To determine whether use of the revised Clinical Institute Withdrawal Assessment (CIWA-Ar) would better guide treatment for the Alcohol Withdrawal Syndrome (AWS), we prospectively studied 16 patients identified as alcohol dependent or with a positive blood alcohol level on admission. All patients were administered the CIWA-Ar. If it was > or = 10, the patient was randomized to a benzodiazepine. If the CIWA-Ar was < 10, the patient was observed and the CIWA-Ar was administered every eight hours for 48 hours. Of the 35 patients screened, 16 were enrolled. Seven patients had a score of > or = 10 and entered a benzodiazepine treatment program. The mean CIWA-Ar score was 18 +/- 10. The remaining nine patients had an initial CIWA-Ar < 10, with a mean score of 3.8 +/- 2.4. We safely withheld detoxification regimens in 9 of 16 patients based on CIWA-Ar scores. The CIWA-Ar may obviate over-utilization of benzodiazepines in patients with AWS.

Hyperprolactinemia associated with risperidone: a case report and review of literature.

This case report describes a 19-year-old Caucasian woman who presented to a state psychiatric facility with symptoms of depression and auditory hallucinations. She was diagnosed with schizoaffective disorder, depressed type, and was treated with risperidone and sertraline. Soon after initiation of drug therapy, the patient developed galactorrhea and dysmenorrhea, and her prolactin level was 171.6ng/mL (normal level 2.8-29.2ng/mL in adult women). Upon discontinuation of risperidone, the prolactin level dropped to 17.2ng/mL within one week. The patient was treated with quetiapine and titrated up to 800mg daily. Repeated prolactin levels continued to be normal during treatment with quetiapine. This case report and others from literature suggest that risperidone is associated with hyperprolactinemia, and that quetiapine is less likely to be associated with hyperprolactinemia.

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.

Enhancing treatment of bipolar disorder using the patient's belief system.

OBJECTIVE: To report a patient with bipolar disorder in whom elements of the patient's belief system were used to foster acceptance of medication treatment. CASE SUMMARY: A 21-year-old white man with bipolar disorder began refusing prescribed divalproex sodium treatment. On consultation, the psychiatric pharmacist identified key elements of the patient's belief system and used this information in developing a plan to foster patient acceptance of lithium carbonate treatment. DISCUSSION: Noncompliance with treatment for bipolar disorder is common, and reluctance to accept initial pharmacotherapeutic intervention often occurs. There are many possible reasons for this phenomenon. Patients may not believe in pharmacotherapy and/or in its benefit, fear adverse reactions, or deny that they are ill. We report a patient in denial of his illness and believing that divalproex sodium was causing adverse effects. A psychiatric pharmacist consultant identified certain patient beliefs that were ultimately important in developing a treatment plan that was acceptable to the patient. The consultant, accompanied by a colleague, used persuasive technique in proposing treatment with the natural product lithium. The patient was discharged within 1 week of accepting the lithium therapy. CONCLUSIONS: When a patient refuses to accept needed treatment, it is important to carefully examine the reasons for this refusal, focusing on the patient's beliefs about the illness and the therapy. Intervention strategies can be developed, using this information, to foster treatment adherence and produce positive outcomes.

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 PANSS, 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.