2007 Edition, N. 2    ORIGINAL RESEARCH    Vol. 39 No. 1Vol. 40, No. 1
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IS ANTIDEPRESSANT SELECTION RATIONAL?
Every clinician faces the daily question of which antidepressant is best for a particular depressed patient. Double-blind studies submitted for U.S. Federal Drug Administration marketing approval include only the “purest” population of patients, which do not adequately address the complexities of many patients. – p.2
THE MANY FACES OF NOVEL ANTIPSYCHOTICS — TWO PERSPECTIVES
.Second-generation antipsychotics are increasingly being used in a broader population of patients and, therefore, for those with comorbid illnesses, adjunctive treatments, or other diagnoses. – p.2
Treatment options for bipolar disorder have rapidly expanded.The authors examined literature on the efficacy of agents, including the mood stabilizers lithium, valproate, lamotrigine, carbamazepine, as well as the atypical antipsychotics olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole. – p.3
THE LONG AND WINDING ROAD: SUBSTANTIATING SSRI EFFICACY
After a few weeks, treatment with most antidepressant drugs leads to a downregulation of the 5 HT2 receptors that allows for increased dopaminergic firing, which is proposed to be decisive for the antidepressant effect. However, serotonin reuptake inhibitors (SRIs) therapeutic mechanisms probably differ between different therapeutic outcomes. – p.3
TWO BEHEMOTHS SQUARE OFF
This article compares the efficacy of olanzapine and risperidone for positive and negative symptoms using an 18-week, randomized, double-blind, crossover design. The hypotheses were that olanzapine would be more efficacious for treating negative symptoms, and that risperidone would be superior in treating positive symptoms. It didn’t quite turn out that way. – ps.3/4
MODERNISM & MEDICINE
Despite their high prevalence, the anxiety disorders are underdiagnosed and undertreated. Benzodiazepines, once the first line of treatment, have been superceded by SSRIs as the treatment of choice. Preclinical studies, however, suggest that CRF antagonists and antagonists of nicotinic, glutamate, 5-HT1A, and NK-1 receptors, may have potential anxiolytic action. Preliminary data suggest that tiagabine, the only available SGRI, may also be beneficial in the anxiety disorders. Further research on these novel agents in anxiety disorders is needed. – p.4
ALSO: THE PRIAPISM/DRUG CONNECTION FIBROMYLGIA, CHRONIC FATIGUE & ADHD – p.4
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RATIONAL ANTIDEPRESSANT SELECTION: APPLYING EVIDENCE-BASED MEDICINE TO COMPLEX REAL-WORLD PATIENTS
Every clinician faces the daily question of which antidepressant is best for a particular depressed patient. Double-blind studies submitted for U.S. Federal Drug Administration marketing approval include only the ?gpurest?h population of patients, and the American Psychiatric Association and other treatment guidelines often do not adequately address the complexities of developmental, family history, psychosocial, medical, and psychiatric comorbidity, and treatment-refractory issues that are seen in routine clinical practice. Long-term trends in depression treatment include ever-expanding choices among drugs, highly specific psychotherapies, and attempts to treat chronic and/or mild cases, with the goal of remission for all patients. We performed literature reviews and attempted to synthesize factors that may be useful in the application of evidence-based medicine in office-based psychiatric practice. We have found that factors influencing antidepressant selection include drug factors (including tolerability, interactions, and cost), depression subtype, psychiatric and medical comorbidity, and stage of life. In addition, patient preference for avoiding certain side effects and personal and family history of treatment response are helpful information. Most patients in the community would not fit strict antidepressant study criteria. Biologic markers predicting treatment response are not yet widely available, so the optimal choice of medication must be guided by detailed history.  Mark Zetin, MD, Cara T. Hoepner, RN, and Lynda Bjornson, PhD.
Psychopharmacology Bulletin.2006;39(1):38-104.
DRUG–DRUG INTERACTIONS ASSOCIATED WITH SECOND-GENERATION ANTIPSYCHOTICS: CONSIDERATIONS FOR CLINICIANS AND PATIENTS
While not always clinically significant, patients with schizophrenia may be at risk for drug (drug-interactions (DDIs) with second-generation antipsychotics. Second-generation antipsychotics are increasingly being used in a broader population of patients and, therefore, for those with comorbid illnesses, adjunctive treatments, or other diagnoses, the clinical significance of DDIs is increasing. This paper reviews currently available data concerning DDIs that occur between second generation antipsychotics, and other medications or substances, when metabolized by the cytochrome P-450 (CYP) family of enzymes. This review will assess the clinical relevance of these interactions for physicians and patients with schizophrenia. EMBASE and MEDLINE searches were conducted (no date restrictions) using the keywords “drug–drug interactions,” “atypical antipsychotics,” “olanzapine,” “ziprasidone,” “quetiapine,” “risperidone,” “aripiprazole,” “clozapine,” “asenapine,” “bifeprunox,” and “paliperidone.” Principal observations: Second-generation antipsychotics are primarily metabolized by CYP enzymes. When coadministered with inducers or inhibitors (psychotropic or nonpsychotropic medications or substances) of CYP enzymes, antipsychotic plasma levels may be reduced or increased, respectively, as a result of DDIs. This can result in a reduced effectiveness of the antipsychotic, or an increased risk of adverse events, respectively. Drugs with a less clinically significant risk for DDIs are a more reliable treatment option for patients in whom drug plasma levels may fluctuate. We concluded that some of the currently available second-generation antipsychotics have a higher potential for DDIs. Agents with a reduced liability for DDIs may be safer treatments as the systemic drug concentration is less likely to seriously increase/decrease when other medications are knowingly or inadvertently co-prescribed or hepatic problems and drug abuse is present.  Robert R. Conley, MD and Deanna L. Kelly, PharmD, BCPP.
Psychopharmacology Bulletin. 2007;40(1):77-97.
MOOD STABILIZERS AND ATYPICAL ANTIPSYCHOTICS: BIMODAL TREATMENTS FOR BIPOLAR DISORDER
Treatment options for bipolar disorder have rapidly expanded, but providing optimal management remains an elusive goal. The authors examined the efficacy of agents with the best clinical evidence supporting their bipolar disorder, including the mood stabilizers lithium, valproate, lamotrigine, carbmazepine, as well as the atypical antipsychotics olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole. Most medications appear to be more effective for symptoms of mood elevation than for symptoms of depression. The efficacy, tolerability, and safety of agents must be considered when making clinical decisions. Several agents, lithium, valproate, olanzapine, quetiapine, and risperidone, can cause problematic weight gain. In addition, the use of atypical antipsychotics has been associated with an risk of metabolic abnormalities such as dyslipidemia, hypergylycemia, and diabetes. In most patients, monotherapy offers
inadequate efficacy. Further investigation of combinations of agents such as mood stabilizers and atypical antipsychotics may yield insights into the potential of combination therapies to enhance clinical outcomes with bipolar disorder.  Terrence A. Ketter, MD, Henry A, Nasrallah, MD, and Andrea Fagiolini, MD.
Psychopharmacology Bulletin. 2006;39(1):120-146.
A MODEL TO EXPLAIN THE THERAPEUTIC EFFECTS OF SEROTONIN REUPTAKE INHIBITORS: THE ROLE OF 5-HT2 RECEPTORS
In this article, it is posited that major depression involves an underfunctioning dopamine system resulting from hypersensitive inhibitory 5-HT2 receptors located on dopaminergic neurons. After a few weeks, treatment with most antidepressant drugs leads to a downregulation of the 5 HT2 receptors that allows for increased dopaminergic firing, which is proposed to be decisive for the antidepressant effect. However, serotonin reuptake inhibitors (SRIs) therapeutic mechanisms probably differ between different therapeutic outcomes. It is hypothesized, that in women, the use of female sex steroids leads to a downregulation of 5-HT2C receptors that contributes to atypical depressive symptoms and premenstrual dysphoria. Consequently, these conditions can be assumed to benefit from the acute increase of serotonergic neurotransmission following ingestion of an SRI rather than the secondary receptor changes, which would explain why there is a therapeutic lag time when SRIs are used to treat depression but not premenstrual dysphoric disorder. The clinical predictions derived from this hypothesis are that 5 HT2 antagonists would be an effective treatment in melancholic depression, have a fast onset of action, speed the onset of SRIs, and can be an effective augmentation for SRI-refractory patients. In contrast, in atypical depression and premenstrual dysphoria, a 5 HT2 antagonist would counteract the therapeutic effect of an SRI, while 5-HT2 agonists have a therapeutic potential. It is suggested that therapeutic response to 5-HT2 antagonists/agonists may be used as a diagnostic tool to dissect subgroups of depression.  Mikael Landen, MD, Phd, and Michael E. Thase, MD.
Psychopharmacology Bulletin. 2006;39(1):147-166.
EFFICACY OF OLANZAPINE AND RISPERIDONE IN SCHIZOPHRENIA: A RANDOMIZED DOUBLE-BLIND CROSSOVER DESIGN
This article compares the efficacy of olanzapine and risperidone for positive and negative symptoms using an 18-week, randomized, double-blind, crossover design. The hypotheses were that olanzapine would be more efficacious for treating negative symptoms, and that risperidone would be superior in treating positive symptoms. Positive and negative symptoms scores improved throughout treatment, regardless of medication type. Differences between the medications were found for negative and general psychopathology rating scales. Overall, olanzapine led to greater improvements in negative symptoms than did risperidone. When each scale was analyzed individually, greater improvements were found for olanzapine on Positive and Negative Symptoms Scale (PANSS) General, PANSS total, and Scale for the Assessment of Negative Symptoms (SANS) attention. A nearly significant trend favoring olanzapine was found for the Calgary Depression Scale. Several negative symptom subscales followed a nonsignificant trend toward olanzapine being more efficacious than risperidone. Thus, there was a very consistent pattern of greater efficacy for olanzapine, particularly for negative symptoms. Despite the small number of subjects, this study shows the potential of a within-subject design to elucidate differences in efficacy.  Jose M. Canive, MD, Gregory A Miller, PhD, Jessica G. Irwin, BS, Sandra N. Moses, PhD, Robert J. Thoma, PhD, J. Christopher Edgar, PhD, Andrea Sherwood, PhD, Fernando Torres,MD, Marianna LaNoue, PhD, Stephen Lewis,MD, Faith M. Hanlon, PhD, Michael P. Weisend, PhD, Valerie Mead, MD, and Vicente B.Tuason, MD.
Psychopharmacology Bulletin. 2006;39(1):105-116.
CURRENT APPROACHES TO THE PHARMACOLOGIC TREATMENT OF ANXIETY DISORDERS
Despite their high prevalence, the anxiety disorders are underdiagnosed and undertreated. Benzodiazepines, once the first line of treatment, have been superceded by SSRIs as the treatment of choice. Preclinical studies, however, suggest that CRF antagonists and antagonists of nicotinic, glutamate, 5-HT1A, and NK-1 receptors may have potential anxiolytic action. Preliminary data suggest that tiagabine, the only available SGRI, may also be beneficial in the anxiety disorders. Further research on these novel agents in anxiety disorders is needed.  David V. Sheehan, MD, MBA, and Kathy Harnett Sheehan, PhD.
Psychopharmacology Bulletin. 2007;40(1):98-109.
PRIAPISM AND QUETIAPINE: A CASE REPORT
Priapism is a ?gpersistent erection not accompanied by sexual desire or stimulation, usually lasting more than six hours and typically involving only the corpora cavernosa.?hHere we report on a gay male patient from our HIV/AIDS mental health clinic who developed serious priapism on quetiapine and recreational amphetamine. Gay men are at high risk for amphetamine use, and as such, this potential association between priapism, quetiapine, and amphetamine use should be considered in making prescription decisions with these patients.  George Harrison, MD, James W. Dilley,MD, Lisa Loeb, MPH, and Kimberly Nelson.
Psychopharmacology Bulletin. 2006;39(1):117-119.
FIBROMYLAGIA, CHRONIC FATIGUE, AND ADULT ATTENTION DEFICIT HYPERACTIVITY DISORDER IN THE ADULT: A CASE STUDY
Adult attention deficit hyperactivity disorder (ADHD) may share common features with fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS). In an outpatient psychiatric clinic, a number of adult patients who presented primarily with symptoms of ADHD, predominately inattentive type, also reported unexplained fatigue, widespread musculoskeletal pain or a pre-existing diagnosis of CFS or FMS. As expected, ADHD pharmacotherapy usually attenuated the core ADHD symptoms of inattention, distractibility, hyperactivity, and impulsivity. Less expected was the observation that some patients also reported amelioration of pain and fatigue symptoms. The utility of ADHD medications in FMS and CFS states may be their innate arousal and enhanced filtering properties. This model supposes that FMS and CFS are central processing problems rather than peripheral disorders of muscles and joints.  Joel L. Young, MD, and Judith C. Redmond, MA.
Psychopharmacology Bulletin. 2007;40(1):118-126.