[Clinically relevant drug interactions with new generation antidepressants and antipsychotics]. / Spezielle Arzneimittelinteraktionen.

Because antidepressants and antipsychotics are commonly described in combination with drugs used to treat comorbid psychiatric or somatic disorders (e.g. anxiolytics, mood stabilizers, cardiovascular drugs, antimicrobial agents), they may be involved in drug interactions. Furthermore, agents such as lithium and atypical antipsychotics may be used to augment the antidepressant response in cases of refractory depression. Based on their mechanisms, drug-drug interactions can be classified either as pharmacokinetic or pharmacodynamic in nature. The well-documented risk of potentially harmful pharmacodynamic drug interactions with first-generation anti-depressants, e.g. monoamine oxidase inhibitors (MAOIs), with regard to the induction of the serotonin syndrome, has contributed to a gradual decline in their use in clinical practise. Second- and third-generation antidepressants have gradually replaced tricyclic antidepressants (TCAs) and MAOIs, mainly because of their improved tolerability and safety profile. The second- and third-generation antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and other compounds with different mechanisms of action. These drugs and also the majority of antipsychotics are metabolized in the liver by the cytochrome P450 (CYP) enzyme system. Therefore, the use of these compounds may be associated with clinically relevant pharmacokinetic interactions with other medications. The knowledge about the CYP metabolism of drugs may be used to guide the selection of an antidepressant or an anti-psychotic with a low drug-drug interaction potential for an individual patient. The aim of the present article is to review drug-interaction potentials with specific focus on second-generation antidepressants (SSRIs), newer antidepressants (SNRIs: venlafaxine and duloxetine; bupropion, mirtazapine, trazodone), novel atypical antidepressants (agomelatine), as well as new generation atypical antipsychotics (aripiprazole, paliperidone).

[Psychopharmacological treatments in childhood and adolescence]. / Psychopharmaka im Kindes- und Jugendalter.

Compared to adults, the use of psychopharmacological substances in childhood and adolescence is significantly more controversial. Often sensation-seeking media reports on the negative effects of psychopharmacological treatments of children and adolescents intensify this controversy on a regular basis. In addition, even pharmacologically trained experts--though frequently without expertise in Child and Adolescent Psychiatry--question the seriousness and thus the demands for treatment of psychiatric disorders in childhood and adolescence. Considering this background evidence based treatment decisions in pediatric psychopharmacology are of utmost importance. Effective psychopharmacotherapy needs to be distinguished from ineffective treatments. The pros and cons of such evidence based treatment approaches ought to be weighted out carefully together with the patients and their families. The aim of this article is to provide a rational and concise foundation for the use of psychopharmacotherapy for clinicians treating children and adolescents as well as to point out the currently best evidence for psychopharmacological treatments of selected disorders in child and adolescent psychiatry.

Epidemiological impact of antidepressant and antipsychotic drugs on the general population.

PURPOSE OF REVIEW: To analyse the prevalence of and sex and age distribution associated with antidepressant and antipsychotic drug exposure in the general population and to highlight recent epidemiological findings concerning specific adverse outcomes associated with drug exposure. RECENT FINDINGS: Epidemiological studies indicate high rates of second-generation antidepressant and antipsychotic drug use in the general population. The use is more prevalent among women than among men, and in older rather than in younger age groups. A new pattern of adverse outcomes has been described in individuals exposed to newer agents, including a possible risk of suicidal acts in adults receiving second-generation antidepressants, the risk of cerebrovascular events in older individuals receiving second-generation antipsychotics and the risk of metabolic disturbances in individuals exposed to specific second-generation antipsychotics. SUMMARY: The assessment of, and attention to, the development of specific adverse reactions in individuals exposed to second-generation psychotropic drugs may improve treatment outcomes.

Efficacy of newer medications for treating depression in primary care patients.

PURPOSE: Several medications have recently been introduced for the treatment of depression. We reviewed the literature to summarize their efficacy in the treatment of depression in adult patients in primary care settings. METHODS: We searched the literature published from 1980 to January 1998 using the Cochrane Collaboration Depression Anxiety and Neurosis Group's specialized registry of 8,451 clinical trials, references from trials and 46 pertinent meta-analyses, and consultation with experts. We included randomized controlled trials of at least 6 weeks' duration that measured clinical outcomes and compared one of 32 newer medications with another newer antidepressant, an older antidepressant, a placebo, or a psychosocial intervention for the treatment of depressed patients in primary care settings. The primary outcome was response rate, defined as the proportion of patients experiencing a 50% or greater improvement in depressive symptoms. RESULTS: There were 28 randomized controlled trials involving 5,940 adult primary care patients with major depression, depression requiring treatment, dysthymia, or mixed anxiety depression. Newer agents, including selective serotonin re-uptake inhibitors, serotonin norepinephrine inhibitors, reversible inhibitors of monoamine oxidase, and dopamine antagonists, were usually compared with tricyclic agents. Average response rates were 63% for newer agents, 35% for placebo, and 60% for tricyclic agents. Newer agents were significantly more effective than placebo [risk ratio = 1.6; 95% confidence interval (CI), 1.2 to 2.1), but similar to tricyclic agents (risk ratio = 1.0; 95% CI, 0.9 to 1.1). Response rates were similar in the different types of depressive disorders, except that two small trials in frail older patients showed no significant effects of newer agents compared with placebo. Dropout rates as a result of adverse effects were 8% with newer agents and 13% with tricyclic agents (P <0.05). CONCLUSIONS: In primary care settings, newer antidepressants are more effective than placebo and have similar efficacy compared with tricyclic agents in the acute treatment of depression. Dropout rates as a result of adverse effects are lower with newer compared with tricyclic agents. Future studies should compare the effectiveness of different therapies among primary care patients with less severe depression and greater medical and psychiatric comorbidity.

A comparison of the direct costs and cost effectiveness of serotonin reuptake inhibitors and associated adverse drug reactions.

BACKGROUND: The economic burden of depression is known to be high and was estimated to be USD 83.1 billion in 2000. Serotonin reuptake inhibitors (SRIs), including both selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), have a superior adverse effect and safety profile relative to traditional agents (e.g. TCAs), and as a result have demonstrated superior cost effectiveness. Although efficacy across the SRIs is similar, the incidence of adverse drug reactions (ADRs) within SRIs remains significant and varies by agent. Patients who experience ADRs from SRIs may seek medical care, require additional treatment, and even discontinue treatment altogether, leading to increased utilisation and cost of therapy. OBJECTIVE: This study estimates the direct cost and cost effectiveness, taking into account the impact of treatment-related ADRs, of eight currently marketed SRIs (citalopram, escitalopram, generic fluoxetine, paroxetine, paroxetine controlled release [CR], sertraline, venlafaxine and venlafaxine extended release [XR]) used as initial treatment for depression. METHODS: A decision analytic model with a 6-month treatment goal was used to estimate the direct cost and cost effectiveness of treatment from the managed care/payer perspective. Estimates of SRI-related ADRs, associated treatments and costs were derived from the US FDA-approved prescribing information and published literature. Efficacy was assumed to be similar across all SRIs. Effectiveness was measured using quality-adjusted life years (QALY) based on EuroQol EQ-5D scores derived from the 2000 Medical Expenditure Panel Survey (MEPS). Censored least absolute deviations (CLAD) regression analysis was used to derive age-adjusted estimates of utility for all health states. Univariate and Bayesian second-order multivariate probabilistic sensitivity analyses were conducted to examine the impact of uncertainty in the parameter estimates. RESULTS: The expected direct cost and cost effectiveness of treatment from least to most expensive were: escitalopram (USD 3891; 0.341), citalopram (USD 3938; 0.340), generic fluoxetine (USD 4034; 0.335), venlafaxine XR (USD 4226; 0.336), sertraline (USD 4250; 0.335), generic paroxetine (USD 4385; 0.332), paroxetine CR (USD 4440; 0.332) and venlafaxine (USD 4613; 0.326). Monte Carlo simulation results suggested that escitalopram was the most likely (77%) to be cost effective for a willingness to pay < or = USD 50,000 per QALY, followed by citalopram (22%), generic fluoxetine (0.3%) and all other SRIs (0%). Sensitivity analyses indicated that the results of the study were robust to the assumptions underpinning the model. CONCLUSIONS: SRI-related ADRs have a significant impact on the direct cost and cost effectiveness of treatment. Escitalopram, with the lowest ADR rate of the SRIs, had the lowest expected treatment cost and greatest effectiveness when compared with citalopram, generic fluoxetine, generic paroxetine, paroxetine CR, sertraline, venlafaxine and venlafaxine XR.

Newer antidepressants. Beyond selective serotonin reuptake inhibitor antidepressants.

This article outlines the use of alternative agents to TCAs and SSRIs. Features of the more commonly used alternative antidepressant agents are outlined. In addition, antidepressant agents that are currently either under development or used in other countries are indicated for completeness because it seems likely that many of these will be introduced in the United States within the next few years. Many of these agents will be used by pediatricians and child psychiatrists for treatment of depression in children, and although much further research is needed, the future for alternative antidepressants and augmenting strategies is extremely promising.

Trends in the use of antidepressants in a national sample of commercially insured pediatric patients, 1998 to 2002.

OBJECTIVE: The aim of this study was to estimate the prevalence of use of prescription antidepressants among children and adolescents by using nationwide data and to examine trends in use from 1998 to 2002. METHODS: Ambulatory prescription claims data for a nationwide random sample of more than 1.9 million life-years of commercially insured children (aged 18 years or younger) for the years 1998, 1999, 2000, 2001, and 2002 were examined retrospectively. The main outcome measure was trend in prevalence of antidepressant use. RESULTS: The overall prevalence of antidepressant use among children increased from 160 per 10000 (1.6 percent) in 1998 to 240 per 10000 (2.4 percent) in 2002, for an adjusted annual increase of 9.2 percent. The growth in the overall prevalence of antidepressant use was greater among girls (a 68 percent increase) than boys (a 34 percent increase). In 2002, antidepressant use was highest among girls aged 15 to 18 years, at 640 per 10000 (6.4 percent). The trend of increasing overall use of antidepressants among children and adolescents appears to have been driven primarily by greater use of selective serotonin reuptake inhibitors. CONCLUSIONS: The growth in the prevalence of use of antidepressant medications among youths appears to be continuing, and the rate of increase between 1998 and 2002 is similar to the rate of increase seen in the period of the second-generation antidepressants (late 1980s to mid-1990s).

Selective serotonin reuptake inhibitor usage patterns as risk factors for hospitalization.

The authors examined how differences in SSRI utilization affect the risk of hospitalization among persons with depression. In particular, they decompose how different types of drug therapy affect hospitalization and how that effect varies with the usage pattern of the drug. Using retrospective medical and pharmacy claims from a Midwestern health maintenance organization, they employed multiple logistic regression analyses of patients newly treated for depression. Their findings were that (a) paroxetine may be a significant risk factor for early discontinuation compared with fluoxetine; and (b) sertraline initiation among stable-use patients may lower the risk of hospitalization. However, initiation on paroxetine or sertraline rather than fluoxetine may increase the risk of hospitalization among patients not exhibiting a stable usage pattern.

[Pharmaco-economic aspects of antidepressants and antipsychotic drugs]. / Pharmakoökonomie von Antidepressiva und Antipsychotika.

This review summarizes results of cost-utility analyses done with newer versus older antidepressants as well as atypical versus conventional/typical neuroleptics/antipsychotics. Following descriptions of the methodological priniciples, the currently available studies (stimulation models) are presented and discussed critically. It can be stated that the economic value of different antidepressants and the atypical neuroleptics can not be decided definitively at the present time due to methodological reasons (e.g. lacking of randomized prospective studies). Increased quality of life of patients and their family seems true for the newer psychotropics, measurement is difficult, however, and a challenge for social and ethical discussions.