Jolene R. Bostwick

Antipsychotic-induced hyperprolactinemia.

Use of antipsychotic agents has been associated with hyperprolactinemia, or elevated prolactin levels; this hormonal abnormality can interfere with the functioning of repro ductive, endocrine, and metabolic systems. As antipsychotic agents are increasingly used for both United States Food and D rug Administratio n‐a ppro ved and nonapprove d indicatio ns, many individuals are at risk for developing antipsychotic‐induced hyperprolactinemia. First‐generation antipsychotics pose the greatest risk of causing this adverse effect; however, second‐generation antipsychotics, particularly risperidone and paliperidone, also often increase prolactin secretion. Hyperprolactinemia has short‐ and long‐term consequences that can seriously affect quality of life: menstrual disturbances, galactorrhea, sexual dysfunction, gynecomastia, infertility, decreased bone mineral density, and breast cancer. Although many of these are definitively connected to elevated prolactin levels, some, such as breast cancer, require further study. Both clinicians and patients should be aware of hyperprolactinemia‐associated effects. To prevent or alleviate the condition, tailoring an antipsychotic drug regimen to each individual patient is essential. In addition, the risk of hyperprolactinemia can be minimized by using the lowest effective dose of the antipsychotic agent. If the effects of prolactin are evident, the drug can be changed to another agent that is less likely to affect prolactin levels; alternatively, a dopamine agonist may be added, although this may compromise antipsychotic efficacy. Additional research is needed to clarify the appropriate level of monitoring, the long‐term effects, and the optimal treatment of antipsychotic‐induced hyperprolactinemia.

A Comparison of the Risk of QT Prolongation Among SSRIs

Objective: To report QT prolongation potential in selective serotonin reuptake inhibitors (SSRIs) in order to advise clinicians on safe use of SSRIs other than citalopram in light of citalopram warnings. Data Sources: Primary literature and case reports were identified through a systematic search. Data from drug manufacturers, package inserts, and the ArizonaCERT database were also utilized. Study Selection and Data Extraction: English-language studies and case reports were included. Data Synthesis: Studies demonstrate possible dose-related clinically significant QT prolongation with escitalopram. Fluoxetine, fluvoxamine, and sertraline at traditional doses demonstrate a lack of clinically significant increases in QTc in the majority of studies. Further, paroxetine monotherapy shows a lack of clinically significant QTc prolongation in all studies. However, case reports or reporting tools still link these SSRIs with QTc prolongation. Fluoxetine, escitalopram, and sertraline used in post–acute coronary syndrome patients did not demonstrate risk of QTc prolongation. Conclusion: For clinicians who choose not to use citalopram due to recent Food and Drug Administration (FDA) recommendations, other antidepressants within this class may be considered. When citalopram is not utilized based on risk factors for TdP, use of escitalopram is not likely the safest alternative. Based on current literature, fluoxetine, fluvoxamine, and sertraline appear to have similar, low risk for QT prolongation, and paroxetine appears to have the lowest risk. However, there are significant limitations in interpreting the studies, including varying definitions of significant QT prolongation. Therefore, choice of an alternative SSRI should be based on individual risk factors for arrhythmias and other patient-specific factors.

Risk of QT/QTc Prolongation Among Newer Non-SSRI Antidepressants

Objective: To review QT prolongation potential with newer nonselective serotonin reuptake inhibitor (non-SSRI) antidepressants. Data Sources: A PubMed literature search was performed from 1982 through June 16, 2014. Search terms included bupropion, desvenlafaxine, duloxetine, levomilnacipran, mirtazapine, venlafaxine, and vilazodone in combination with each of the following terms: cardiac toxicity, QTc prolongation, QT prolongation, torsades de pointes, and TdP. Study Selection and Data Extraction: English-language human studies, case reports, package inserts, manufacturer electronic communications, and ArizonaCert database were utilized. Data Synthesis: Rare QT prolongation has been reported with venlafaxine at therapeutic doses and in overdose. Bupropion has also been linked to QT prolongation in overdose situations. In elderly patients with a variety of high-risk comorbidities, mirtazapine did demonstrate higher odds of sudden cardiac death and ventricular arrhythmias when compared with paroxetine. Largely because of a lack of available data, existing studies fail to demonstrate QT prolongation with desvenlafaxine, duloxetine, levomilnacipran, and vilazodone. Conclusion: Based on the current literature, risk of QT/QTc prolongation with the majority of newer non-SSRI antidepressants at therapeutic doses is low. The highest risk for QT prolongation appears to exist in overdose situations with venlafaxine and bupropion. Given the few to nonexistent controlled studies and confounding variables present in case reports, it is difficult to draw conclusions on QT prolongation risk with many of the newer non-SSRI antidepressants.

Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment-resistant depression.

Treatment‐resistant depression (TRD) is a major health concern. More than 40% of patients treated for major depressive disorder with an appropriate antidepressant dose for an adequate duration fail to respond. Further, approximately half of adults with major depressive disorder fail to achieve sustained remission despite various medication trials. The utilization of monoamine oxidase inhibitors (MAOIs) for the treatment of depression in clinical practice today is low due to their widely known adverse effects, some of which may be life threatening, and the risk for dietary and drug interactions. For these reasons, MAOIs are not recommended to be prescribed along with other antidepressants or certain prescription or nonprescription drugs. Pharmacologic options are limited for individuals with TRD, however, and there is a paucity of data on the efficacy of MAOIs in combination with other antidepressants for the management of TRD. We performed a search of the PubMed database (inception through January 25, 2015) to identify cases that illustrate the potential utility, as well as risks, of combination treatment with MAOIs and other antidepressants for the management of TRD; 18 articles met the criteria for our search. In addition, we performed a retrospective case series by reviewing the medical records of 29 adults treated for depression with an MAOI plus another psychotropic agent (an antidepressant or stimulant medication) between 2003 and 2012 at a large Midwestern teaching hospital. We compared the findings of the published experience with our local experience to allow for more informed decisions regarding pharmacotherapy in patients with TRD. We separated the local experience into two groups: 15 cases with the selective MAO type B inhibitor selegiline combined with medications presumed to increase the risk of serotonin syndrome and 14 cases with nonselective MAOIs (phenelzine and tranylcypromine) combined with other contraindicated medications. Although risks of combination treatment certainly exist with selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, or clomipramine, the current literature supports cautious use of combining MAOIs with other antidepressants in patients with TRD who have failed multiple treatment modalities. In addition, the data from the 29 patients receiving combination therapy with an MAOI and another antidepressant or stimulant medication revealed that 21% improved significantly, with no complications. This case series and literature review suggest that when used under close supervision and under the care of an experienced clinician in psychiatry, combination therapy may be a consideration for the management of TRD in patients not responding to monotherapy or other combinations of antidepressants.

Alternate Routes of Administration of Antidepressant and Antipsychotic Medications

Objective: To review the administration of antidepressant and antipsychotic medications via inhaled, intranasal, buccal, sublingual, transdermal, and rectal routes. Data Sources: A PubMed search was conducted for all data through March 31, 2015 to identify pertinent literature. Search terms included the generic name of each antidepressant and antipsychotic medication in combination with the following terms: alternate routes of administration, inhaled, intranasal, buccal, sublingual, transdermal, and rectal. Study Selection and Data Extraction: English-language case reports, studies, and reviews describing medication administration in human subjects were included. Data Synthesis: Commercially available products that use an alternative route of administration include loxapine for inhalation, asenapine for sublingual administration, and selegiline for transdermal administration. Case reports and studies describe intranasal, sublingual, and transdermal routes of administration of antipsychotic medications as well as buccal, sublingual, transdermal, and rectal administration of antidepressant medications. The concordance between the physicochemical properties possessed by some antipsychotic and antidepressant agents and the physicochemical properties required for nontraditional routes of administration suggest that administration via alternative routes may be feasible for some of these drugs. Further exploration of drug absorption via alternative routes in addition to consideration of patient and formulation factors may yield improvements in medication therapy for patients with psychiatric illnesses. Conclusions: For patients unable to tolerate oral or injectable therapy, administration of psychotropic medications via nontraditional routes may be feasible. The development of alternative routes of drug delivery could prevent discontinuation of needed medication therapy.

Evaluation of a computer‐based intervention to enhance metabolic monitoring in psychiatry inpatients treated with second‐generation antipsychotics

What is known and Objective:  Second‐generation antipsychotics (SGAs) play an important role in the pharmacologic management of various psychiatric conditions. Use of these medications has been associated with metabolic complications. Adherence to guideline‐recommended monitoring is suboptimal. We evaluated the effect of a computerized physician order entry (CPOE) pop‐up alert designed to improve rates of laboratory metabolic monitoring of patients treated with SGAs on a University Hospital inpatient psychiatry unit.

The Effects of Cannabis on Inpatient Agitation, Aggression, and Length of Stay

ABSTRACT Objective: This study examines the association between cannabis use and the hospital course of patients admitted to the psychiatric inpatient unit with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder. Many confounding variables potentially contribute to the clinical presentation of hospitalized patients in the psychiatric unit. Illicit drug use, in particular, has been associated with acute agitation, and questions can be raised as to what lasting effects drug use prior to admission may have throughout a patients hospital stay. Methods: Subjects with a discharge diagnosis of bipolar disorder, schizophrenia, schizoaffective disorder, or psychosis not otherwise specified (N = 201) were retrospectively identified, and those with positive results of urine drug screen for cannabis on admission were compared to negative counterparts. Agitation and aggression were measured using an adaptation of the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC). These markers were also quantified by comparing charted episodes of restraint and seclusion and administration of as needed medications, such as benzodiazepines and antipsychotics. Results: Positive urine drug screen results for cannabis was correlated with young (p = .001) males (p = .003) with bipolar disorder (p = .009) exhibiting active manic symptoms (p = .003) at the time of admission. Cannabis use was further associated with a shorter length of stay (p = .008), agitation triggering adapted PANSS-EC nursing assessments (p = .029), and oral medications as needed (p = .002) for agitation. Conclusions: Cannabis use, as defined by positive urine drug screen results, was more common in patients with bipolar disorder and was accompanied by a higher incidence of inpatient agitation. Although these patients also had short hospital lengths of stay, there was no clear relationship between level of agitation and length of stay across all patient groups. One possible explanation for patients with bipolar disorder experiencing short lengths of stay is that their source of agitation may be more closely related to a complex effect of cannabis use rather than a sole etiology of mental illness. Inpatient clinicians should be aware of patient cannabis use proximate to admission.

Effectively implementing FDA medication alerts utilizing patient centered medical home clinical pharmacists

FDA medication alerts can be successfully implemented within patient centered medical home (PCMH) clinics utilizing clinical pharmacists. Targeted selection of high-risk patients from an electronic database allows PCMH pharmacists to prioritize assessments. Trusting relationships between PCMH clinical pharmacists and primary care providers facilitates high response rates to pharmacist recommendations. This health system approach led by PCMH pharmacists provides a framework for proactive responses to FDA safety alerts and medication related quality measure improvement.

Beginning your career in academia at a new college of pharmacy.

According to the Accreditation Council for Pharmacy Education (ACPE) annual report for January 15, 2007, to January 14, 2008, there were 106 accredited pharmacy schools in the United States: 90 full, 10 candidate, and 6 precandidate status.[1][1] Opportunities in academia at new and existing schools

Procarbazine and antidepressants: a retrospective review of the risk of serotonin toxicity

Procarbazine is an anticancer agent that also inhibits monoamine oxidase, an enzyme responsible for the metabolism of various catecholamines, including serotonin.