Monotherapeutic Treatment Research Articles

Predicting Response to Psychopharmacological Treatment: Survey of Recent Results *

Treatment with antidepressants and antipsychotics, though effective, is unspecific as agents that differ greatly in their biochemical and pharmacological actions have virtually the same efficacy. Half of the patients with initial improvement show incomplete response, while a large proportion of patients exhibit a refractory clinical picture which is resistant to all treatment modalities. Our analyses were based on a reference study of 2,848 depressive inpatients under monotherapeutic treatment with 7 different antidepressants or placebo, along with a naturalistic study of depressive and schizophrenic patients (296 inpatients, 363 outpatients) under today's "standard" polypharmaceutic treatment regimens. The empirical data suggested the following predictors of response: (1) severity at baseline, (2) early onset of improvement, (3) unwanted side-effects, and (4) medical comorbidity. A combination of these predictors with Therapeutic Drug Monitoring (TDM) methods has direct clinical relevance. Evidence-based approaches to personalized treatment help improving the unsatisfactory situation patients and clinicians are faced with, given today's incomplete treatments and the fact that the mechanisms by which antidepressants and antipsychotics ultimately exert their therapeutic effects are only marginally understood.

Pharmakologische Kombinationsbehandlung bipolarer Störungen

In the course of time, the treatment regime of bipolar disorder has changed: in mild cases of manic and depressive episodes, monotherapeutic approaches are still commonly used. Besides the use of the common agents like lithium, valproatic acid and carbamazepine, other agents such as atypical antipsychotics (AAP) are used more frequently. For the therapy of manic episodes, most of the usual AAP are approved; some of them are or will be approved in the near future even for the continuation therapy and for depressive episodes. For moderate and severe courses of depressive or manic episodes, combination therapy strategies are used more often. Combination strategies seem to be more effective than monotherapeutic treatments, because of faster effects and better tolerance. In a lot of studies, these positive effects and advantages in contrast to monotherapeutic treatments could be proven. In this review article, studies and results with the focus on combination therapy will be summarised to recommend the "state-of-the-art"-treatment for bipolar disorder.

Adjunctive Versus Monotherapeutic Treatment for Schizophrenia: Addressing Antipsychotic Side Effects

Back to table of contents Previous article Next article Letters to the EditorFull AccessAdjunctive Versus Monotherapeutic Treatment for Schizophrenia: Addressing Antipsychotic Side EffectsMONICA HAZRA B.Sc. Phm, R.Ph.DAVID C. MAMO M.D., M.Sc.GARY REMINGTON M.D., Ph.D., F.R.C.P.C.,MONICA HAZRA B.Sc. Phm, R.Ph.Search for more papers by this authorDAVID C. MAMO M.D., M.Sc.Search for more papers by this authorGARY REMINGTON M.D., Ph.D., F.R.C.P.C.Search for more papers by this author,Published Online:1 Mar 2008https://doi.org/10.1176/appi.ajp.2007.07111738AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To The Editor: In the article by Joo-Cheol Shim, M.D., Ph.D., et al., published in the September 2007 issue of the Journal, aripiprazole was added to haloperidol to evaluate the beneficial effects on haloperidol-induced hyperprolactinemia. The authors pointed out that switching is “not always possible in clinical practice, especially if the patient has responded well to the antipsychotic that produced the hyperprolactinemia” ( 1 , p. 1404). The addition of aripiprazole significantly decreased prolactin levels and improved negative symptoms, sleep, and extrapyramidal side effects. The authors attributed these effects to aripiprazole’s unique mechanism(s) of action (2) . We do not take issue with the scientific merit of this study but are concerned with the clinical implications, specifically the apparent promotion and justification of the adjunctive use of aripiprazole. Well-controlled clinical studies have not supported the use of antipsychotic polypharmacy, and this practice has been associated with increased adverse effects (3 , 4) , premature death (5) , and unnecessary economic demands (6) . Good clinical practice argues for the fewest medications possible and, in the case of treatment with antipsychotics, advocates for the adjunctive use of antipsychotics as a last resort (7) . As a class, the newer antipsychotics have afforded us advantages in decreasing extrapyramidal symptoms, lowering prolactin levels, and reducing the risk of tardive dyskinesia (2 , 7 , 8) . Furthermore, contrary to what is stated in the article by Dr. Joo-Cheol Shim et al., switching antipsychotic drugs, including a switch from haloperidol to aripiprazole, has previously been shown to be safe and effective (9) . Toronto, Ontario, CanadaDr. Remington has received research funding from NARSAD, the Stanley Medical Research Institute, Novartis, and Merck (Germany). Drs. Hazra and Mamo report no competing interests.This letter (doi: 10.1176/appi.ajp.2007.07111738) was accepted for publication in November 2007.

The Incretin Mimetic Exenatide as a Monotherapy in Patients with Type 2 Diabetes

Exenatide is an adjunctive therapy for type 2 diabetes, and preliminary evidence suggests that its glucoregulatory effects may be similar in the absence of oral therapy. Study A was a randomized, double-blind, placebo-controlled study of 99 patients with type 2 diabetes that received either 10 microg twice-daily, 10 microg once-daily, or 20 microg once-daily exenatide or placebo for 28 days in the absence of background pharmacotherapy. Study B was an open-label extension of a short-term study of 127 patients with type 2 diabetes treated with metformin or diet and exercise. Patients received exenatide 5 microg twice-daily for 4 weeks followed by 10 microg for 26 weeks. Subjects treated with metformin continued oral therapy. Monotherapeutic treatment with 10 microg of exenatide twice-daily for 28 days resulted in significant mean reductions in glycosylated hemoglobin (A1C) of -0.4 +/- 0.1% and fasting plasma glucose of -36.1 +/- 11.0 mg/dL compared to increases of +0.2 +/- 0.1% and +11.0 +/- 12.7 mg/dL with placebo. Self-monitored blood glucose profiles showed significant mean reductions in daily blood glucose concentrations in exenatide-treated patients compared to placebo. Exenatide treatment for 30 weeks in an open-label extension study resulted in similar mean reductions from baseline in A1C and body weight in patients treated with diet and exercise alone (-1.0 +/- 0.2% and -4.3 +/- 1.3 kg, respectively) as those treated on a background of metformin (-0.9 +/- 0.1% and -3.7 +/- 0.5 kg, respectively). In both studies, the most frequent adverse events were gastrointestinal and predominantly mild to moderate in intensity. Incidence of mild-to-moderate hypoglycemia was low, with no severe hypoglycemia. Exenatide twice-daily monotherapy resulted in glycemic improvements and reductions in body weight comparable to that of exenatide combination therapy with metformin in patients with type 2 diabetes.

Polytherapy in the preventive and acute treatment of migraine: fundamentals for changing the approach

The pathophysiology of migraine is complex and involves multiple neurophysiological pathways. Monotherapeutic approaches for migraine are the rule but many patients discontinue their medications owing to lack of efficacy. Polytherapy may provide a rational strategy for some of these individuals. Herein, we review the basis of polytherapy treatment for migraine. We suggest that refractory patients, with previous failure to single agents, may benefit from the use of a two- or three-drug regimen combining medications that target different neurotransmitter systems. In addition, those patients with high recurrence rates or not presenting pain free at 2 h and/or sustained pain free at 24 h may also respond better to combination therapy suited to their individual profile, which must include nonsteroidal anti-inflammatory agents plus a triptan or a gastrokinetic drug. The three-drug regimen may also be considered. Finally, changing the time medicine is taken (before the development of central sensitization and allodynia cutanea) and switching the choice of formulations to non-oral potentially achieves a better response and can be determined individually. Although highly speculative, these hypotheses could stimulate further controlled studies to support changing the current paradigm of monotherapeutic migraine treatment in some patients.

The effects of antipsychotic treatment on quality of life of schizophrenic patients under naturalistic treatment conditions: An application of random effect regression models and propensity scores in an observational prospective trial

The study examines the effect of different types of antipsychotic treatment on the health related quality of life (HRQL) of people with schizophrenia under naturalistic outpatient treatment conditions. In a prospective study design, 307 schizophrenic patients were followed over a period of 2.5 years. HRQL, clinical characteristics, and type of antipsychotic medication were assessed five times every 6 months. HRQL was assessed by the SF-36. Random effect regression models were computed for the SF-36 mental (MCS) and physical (PCS) component scores. Propensity scores were included in the regression models to reduce a possible sample selection bias. Monotherapeutic treatment with new atypical neuroleptic drugs had a more positive effect on the mental health related quality of life (MCS) in comparison to treatment with polypharmacological treatment but not with oral conventional antipsychotics. Monopharmaceutical treatment with depot-antipsychotic drugs had a more positive effect on the physical health related quality of life (PCS) in comparison to polypharmacological treatment. Study results indicate that atypical antipsychotic drugs are not superior to conventional antipsychotics with regard to the effect on QOL. However, monopharmaceutical treatment can be assumed to be more effective in improving mental and physical related QOL than polypharmaceutical treatment.

Combined therapy: what does acamprosate and naltrexone combination tell us?

Relapse prevention treatment with both acamprosate and naltrexone has been shown to be efficacious in the treatment of alcoholism. Whereas both compounds act pharmacologically differently, there is up to now only limited evidence as to whether combined treatment is efficacious and pharmacologically safe. It remains to be answered whether data justify the combination of both drugs in clinical practice. Review of the three pre-clinical and four clinical studies that have been published to date on either combined tolerability or efficacy. Data available up to now show no occurrence of severe adverse events during combined treatment. Diarrhoea and nausea were shown to be the most significant side-effects. Whereas pre-clinical studies regarding efficacy of combined treatment are not yet conclusive, clinical data show the superiority of combined treatment compared with both placebo and acamprosate monotherapy. The synergistic effect of combined treatment remained after 12 weeks of drug-free follow-up. The combination of acamprosate with naltrexone in a clinical sample seems to be efficacious and safe. Numerous alcohol dependent patients could benefit, particularly those that responded insufficiently on monotherapeutic treatment with either acamprosate or naltrexone.

Quetiapine in the Treatment of Borderline Personality Disorder

Affective dysregulation, impulsivity and cognitiveperceptual difficulties are the psychopathological nuclear dimensions of Borderline Personality Disorder (BPD). Psychopharmacological treatment may become necessary during episodes of acute decompensation in which suicidal or self-destructive behaviour erupts. Some classes of psychotropic drugs have demonstrated efficacy in diminishing symptom severity and optimising functioning, such as antidepressants, mood stabilizers, benzodiazepines, opiate antagonists and antipsychotics. Conventional antipsychotics are the best-studied psychotropic medications for BPD, but nonadherence is often due to their severe side effects. Preliminary data reveal efficacy of atypical antipsychotics in BPD. We describe the impact of the novel antipsychotic drug quetiapine on severe self-mutilation in two female patients with the diagnoses of BPD. In both cases, monotherapeutic treatment with quetiapine was well tolerated and resulted in a marked improvement of impulsive behaviour and, over time, overall level of function. Though promising, our findings have to be regarded as preliminary. Due to the overall paucity of data there is still insufficient evidence to make a strong recommendation concerning continuation and maintenance therapy with atypical antipsychotics in BPD. Thus, there is a clear need for further controlled studies to evaluate pharmacological treatment options for this disorder.

Análisis de coste­minimización del tratamiento antiepiléptico en monoterapia en pacientes con epilepsia de reciente diagnóstico: situación en España

To analyze the cost of monotherapeutic treatment of patients with newly diagnosed epilepsy. We analysed the cost of treatment with lamotrigine (LTG), carbamazepine (CBZ), phenytoin (PHT) and valproic acid (VPA) using published data regarding the efficacy and tolerability of comparative clinical trials of monotherapy. We established a model of treatment for newly diagnosed patients during the first 12 months after diagnosis. A panel of doctors reached a consensus on the use of resources, costs and model of treatment in Spain. We made a cost minimization analysis for economic assessment of the data based on the fact that randomized trials indicated that CBZ, LTG, PHT and VPA ware of similar efficacy. Analysis was done as 'intention to treat'. Only direct medical costs were considered. In Spain treatment with LTG is twice or three times as expensive as treatment with the other drugs. Sensitivity analysis showed that variations in the interval of use of resources and of costs (defined by the panel of doctors) did not significantly alter the results. Treatment with LTG is more expensive than treatment with the classical drugs. In view of the methodological limitations of this study, further analysis is necessary, particularly of the methodology of cost-benefit, to evaluate the economic impact of the new antiepileptic drugs and determine whether their use is justified as drugs of first choice.

Open Comparative Long-term Study of Vigabatrin vs Carbamazepine in Newly Diagnosed Partial Seizures in Children

To compare vigabatrin with carbamazepine as monotherapy in newly diagnosed children with partial epilepsy in order to evaluate the efficacy and tolerability of both drugs. Open and randomized with a 2-year follow-up period. The Infantile Neuropsychiatric Division of the Regional Pediatric Hospital, Ancona, Italy. Seventy children with newly diagnosed partial epilepsy were treated with vigabatrin (38 patients) or carbamazepine (32 patients). Vigabatrin, 50 to 60 mg/kg per day, or carbamazepine, 15 to 20 mg/kg per day, split into twice-a-day doses. The efficacy and tolerability of vigabatrin were compared with those of the standard treatment (carbamazepine) for this patient group. The efficacy of vigabatrin and carbamazepine was similar, with the suggestion of a better side effect profile with vigabatrin. Vigabatrin monotherapy should be considered as a monotherapeutic treatment option in patients with newly diagnosed epilepsy. However, more studies are needed to evaluate other issues of concern, such as the cognitive and behavioral adverse effects of antiepileptic drugs, to determine the most suitable therapy.

Open evaluation of amlodipine in the monotherapeutic treatment of mild to moderate hypertension in nigerian patients

The efficacy and tolerability of amlodipine, a new second-generation dihydropyridine calcium channel blocker, as antihypertensive monotherapy was evaluated in an open 12-week study in 24 hypertensive patients. Treatment with amlodipine was started at 5 mg daily after a 2-week washout period and adjusted to 10 mg daily if the patient's diastolic blood pressure was >90 mmHg after 2 weeks of therapy. The response rate was 91%, and blood pressure was normalized in 72.7% of patients after 12 weeks of therapy. The blood pressure profiles were similar in the supine, sitting, and standing positions, with a decrease in mean supine blood pressure from 180.7 ± 3.7 mmHg/113.1 ± 1.3 mmHg at baseline to 146.3 ± 2.7 mmHg/88.0 ± 1.2 mmHg at 12 weeks. A slight but significant initial increase in heart rate was observed in all positions during the first week of therapy, but no further increase was seen beyond the first week, even though doses were subsequently increased. Adverse experiences were mild and transient and included frequent micturition, pedal edema, headache, and poor erection. The results suggest that once-daily amlodipine is an effective and well-tolerated monotherapy for the treatment of hypertension.

A Double-Blind, Parallel, Comparative Evaluation of Amlodipine vs. Captopril in the Monotherapeutic Treatment of Mild and Moderate Essential Hypertension

A double-blind, parallel, comparative study of the antihypertensive efficacy and safety of once-daily oral doses of amlodipine (5-10 mg/day) vs. twice-daily oral doses of captopril (25-50 mg twice daily) in adult patients with mild or moderate essential hypertension (supine diastolic blood pressure of 95-115 mm Hg) was undertaken in two hospital centers. Interim analysis of data from 40 patients shows that amlodipine and captopril both significantly (p < 0.05) reduced blood pressure compared with baseline. Nineteen of 21 (90.5%) amlodipine-treated patients and 15 of 19 (78.9%) captopril-treated patients had their diastolic blood pressure "normalized" (< 90 mm Hg) with mean final doses of 8.2 and 76.7 mg/day, respectively. At the final visit, there were no statistically significant differences between the two treatment groups in either mean supine or standing blood pressure. Minor nonsignificant changes in standing heart rate were observed in both treatment groups. Seven of the 21 amlodipine-treated patients and 3 of the 19 captopril-treated patients reported adverse experiences. No patients in either treatment group discontinued due to adverse events; one patient in the amlodipine group required a dose reduction. These interim data indicate that the overall efficacy and safety profiles of these two drugs are comparable.

Open Evaluation of Amlodipine in the Monotherapeutic Treatment of Systolic Hypertension in the Elderly

The antihypertensive efficacy and safety of amlodipine (5-10 mg once daily for 10 weeks) was assessed in elderly patients with primary systolic hypertension (average sitting and standing systolic blood pressure > or = 160 mm Hg and diastolic blood pressure < or = 95 mm Hg). Interim analysis of data from 25 patients shows that amlodipine treatment produced significant decreases in sitting blood pressure (-26.8/-11.4 mm Hg; p < 0.05). Efficacy assessments after 8 weeks of therapy showed 15 of 21 (71.4%) evaluable patients were considered therapeutic successes with amlodipine (defined as a fall from baseline in sitting systolic blood pressure of > or = 20 mm Hg or to < or = 150 mm Hg with a fall of > or = 10 mm Hg). Of the six evaluable patients who were not considered therapeutic successes using this definition, three had clinically beneficial falls in systolic blood pressure of 16-18 mm Hg. Fourteen patients were considered therapy successes on the basis of assessments taken 48 h postdose at the end of the study. Investigators' overall impression of efficacy was excellent or good in 21 patients (84%). Amlodipine treatment had no significant effect on heart rate. Amlodipine was generally well tolerated, with no patients being withdrawn due to side effects. Investigators' evaluation of toleration was excellent or good in 22 patients (88%).

An Open, Parallel, Comparative Evaluation of Amlodipine and Nitrendipine in the Monotherapeutic Treatment of Mild and Moderate Essential Hypertension

Summary: The efficacy and safety of the dihydropyridine calcium antagonists amlodipine and nitrendipine as single-agent therapy of mild to moderate hypertension were compared in an open, parallel-group study. Interim analysis of data from 74 patients (43 male, 31 female) from an expected final total of 96 patients is reported. Amlodipine normalized blood pressure (≤90 mm Hg) in 94.7% of patients with a mean final dose of 8.3 mg/day, compared with normalization of blood pressure in 83.3% of patients treated with nitrendipine with a mean final dose of 28.3 mg/day. Only nitrendipine produced a statistically significant increase in heart rate after 2 and 4 weeks of therapy. Nitrendipine-treated patients reported more adverse events (47.2%) than the amlodipine-treated group (26.3%). Two patients from the nitrendipine group discontinued treatment due to treatment-related adverse events and one patient required a dose reduction. In the amlodipine-treated group, all adverse events were mild to moderate and dose reduction was required in one patient. In conclusion, although amlodipine and nitrendipine have comparable antihypertensive efficacy, in this study amlodipine was associated with fewer adverse effects.

An Open, Parallel, Comparative Evaluation of Amlodipine and Nitrendipine in the Monotherapeutic Treatment of Mild and Moderate Essential Hypertension

The efficacy and safety of the dihydropyridine calcium antagonists amlodipine and nitrendipine as single-agent therapy of mild to moderate hypertension were compared in an open, parallel-group study. Interim analysis of data from 74 patients (43 male, 31 female) from an expected final total of 96 patients is reported. Amlodipine normalized blood pressure (< or = 90 mm Hg) in 94.7% of patients with a mean final dose of 8.3 mg/day, compared with normalization of blood pressure in 83.3% of patients treated with nitrendipine with a mean final dose of 28.3 mg/day. Only nitrendipine produced a statistically significant increase in heart rate after 2 and 4 weeks of therapy. Nitrendipine-treated patients reported more adverse events (47.2%) than the amlodipine-treated group (26.3%). Two patients from the nitrendipine group discontinued treatment due to treatment-related adverse events and one patient required a dose reduction. In the amlodipine-treated group, all adverse events were mild to moderate and dose reduction was required in one patient. In conclusion, although amlodipine and nitrendipine have comparable antihypertensive efficacy, in this study amlodipine was associated with fewer adverse effects.