Inhibition of serotonin reuptake by antidepressants and cerebral microbleeds in the general population.

BACKGROUND AND PURPOSE: Serotonin reuptake inhibiting antidepressants decrease platelet aggregation. This may cause an increased risk of intracerebral hemorrhage. However, the risk of subclinical microbleeds, which are highly prevalent in middle-aged and elderly people, is unknown. We studied whether serotonin reuptake inhibiting antidepressants increase the frequency of cerebral microbleeds and secondarily whether they lower the presence of ischemic vascular damage. METHODS: Within the population-based Rotterdam Study, information on antidepressant use was obtained from continuously monitored pharmacy records. Brain MRI was available in 4945 participants (55% women, mean age 64 years) between 2005 and 2011. We categorized antidepressants based on affinity for the serotonin transporter: high, intermediate, or low. Microbleeds (presence and location) and ischemic lesions (lacunes, white matter lesions) were rated on MRI. Logistic and linear regression, adjusted for age, sex, depressive symptoms, and cardiovascular risk were used to study the association of antidepressants with microbleeds and ischemic vascular lesions. RESULTS: Antidepressant use with strong serotonin reuptake inhibition was not associated with microbleed presence (odds ratio compared with nonuse, 1.03; confidence interval, 0.75-1.39) irrespective of microbleed location in the brain. Exclusion of antithrombotic users or persons with cortical infarcts did not change our results. Furthermore, serotonin reuptake inhibition was not related to ischemic vascular brain damage. CONCLUSIONS: In the general population, use of serotonin reuptake inhibiting antidepressants is not related to presence of cerebral microbleeds. This strengthens the idea that the platelet inhibitor effects of antidepressant drugs with affinity for serotonin are minimal and further supports the safety of selective serotonin reuptake inhibitors for nongastrointestinal bleedings.

Metabolic kinetics of 5-hydroxytryptamine and the research targets of functional gastrointestinal disorders.

5-Hydroxytryptamine (5-HT) is an important neurotransmitter in both the central and enteric nervous systems. It has diverse functions in regulating gastrointestinal motility and visceral sensitivity, emotion, appetite, pain and sensory perception, cognition, sexual activity and sleep. These functions are mainly associated with the metabolic kinetics of 5-HT in different tissues. Tryptophan hydroxylase is the rate-limiting enzyme and modulates serotonin synthesis. Vesicular monoamine transporter 1 plays a role in 5-HT storage and release. Degradation of 5-HT is mediated by monoamine oxidase-A. All these factors influence the action of 5-HT in vivo. Functional gastrointestinal disorders (FGIDs) are characterized by a series of symptoms including abdominal pain, diarrhea, constipation, anxiety and depression, in the absence of identifiable structural or biochemical abnormalities. They are frequently accompanied by changed gut motility or visceral sensitivity. An increasing body of research has found FGIDs to be closely associated with 5-HT, and drugs such as citalopram, paroxetine, venlafaxine, alosetron, tegaserod, prucalopride and mosapride have all been developed or discovered from the perspective of the metabolic kinetics of 5-HT. This review discusses the relationship between the metabolic kinetics of 5-HT and research targets in the field of FGIDs and suggests areas of future study that may be useful for understanding these disorders and identification of potential therapeutic targets.

Effects of SNS activation on SSRI-induced sexual side effects differ by SSRI.

Selective serotonin reuptake inhibitors (SSRIs) are associated with significant sexual side effects. By definition, all SSRIs increase overall serotonin (5HT) by binding to serotonin autoreceptors (5HT(IA)); however, each SSRI has a unique portfolio of secondary binding properties to other neurotransmitters such as norepinephrine (NE). As 5HT(IA) receptors mediate NE neurotransmission, SSRIs that are highly selective for 5HT(IA) are more likely to reduce NE efficiency; however, in SSRIs that are less selective for 5HT(IA), this could be counteracted by secondary binding to NE. Norepinephrine is the major neurotransmitter of the sympathetic nervous system (SNS), which has been shown to mediate genital arousal in women; thus, it is possible that increasing SNS activity in women taking SSRIs that are highly selective for 5HT(IA) may counteract sexual side effects in those women. To test this hypothesis, we conducted a reanalysis of Meston (2004)'s 8-week, double-blind, cross-over, placebo-controlled study of the effects of ephedrine (50 mg taken 1 h prior to sexual activity) on self-reported sexual functioning of women taking paroxetine (N = 5), sertraline (N = 7), or fluoxetine (N = 7). As predicted, women taking SSRIs, which are highly selective for 5HT(IA) (sertraline, paroxetine), showed improvement in sexual arousal and orgasm. By contrast, women taking SSRIs, which are less selective for 5HT(IA) relative to NE (fluoxetine), showed no change or decrease in sexual functioning. These findings have implications for treating certain SSRI-induced sexual side effects.

[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.

[Multimodal serotonergic antidepressants]. / Mul'timodal'nye serotoninergicheskie antidepressanty.

Based on the original literature, the author for the first time describes a history of selective serotonergic antidepressants simultaneously inhibiting the serotonin reuptake and directly interacting with serotonin receptors. A history of creation and introduction of their main representatives is presented. A history of investigation of their neurochemical activity is analyzed in details. The history of the evolution of their classifications is systemized. The data presented suggest the rationale for unifying all selective serotonergic antidepressants, simultaneously inhibiting the serotonin reuptake and directly interacting with serotonin receptors (trazodone, etoperidone, nefazodone, vilazodone, vortioxetine), in one group of 'multimodal serotonergic antidepressants'. The expediency to include this group in the modern neurochemical classification of nootropic drugs is substantiated.

Allosteric modulation of the effects of the 5-HT reuptake inhibitor escitalopram on the rat hippocampal synaptic plasticity.

The present in vivo electrophysiological studies in anesthetized rat were undertaken to assess the effects of the selective serotonin (5-HT) reuptake inhibitor (SSRI) escitalopram alone or in combination with the R-citalopram (the S- and R-enantiomers of citalopram), on both long-term potentiation (LTP) in the CA(1) region of dorsal hippocampus and spontaneous firing activity of dorsal raphe (DR) 5-HT neurons. At the postsynaptic level, neither escitalopram (10 mg/kg, i.p.) nor R-citalopram (20 mg/kg, i.p.) modified basal synaptic transmission but only escitalopram impaired LTP expression. Importantly, R-citalopram counteracted significantly the escitalopram-induced decrease of LTP. At the pre-synaptic level, escitalopram (25-75 microg/kg, i.v.) dose-dependently suppressed the spontaneous firing activity of DR 5-HT neurons and this suppressant effect was significantly prevented by a prior injection of R-citalopram (10 mg/kg, i.p.). These results support a role of allosteric binding sites of 5-HT transporter in the regulation of long-lasting CA(1) synaptic plasticity and DR 5-HT neuronal firing activity.

History repeats itself: pharmacodynamic trends in the treatment of anxiety disorders.

The original treatment indicated for those suffering from neurotic anxiety was to employ psychotherapy to facilitate changes in behavior and coping with stressful events. A spectrum of somatic treatments "from cathartics and emetics to opium and "strengthening tonics", from atropine and digitalis to potassium bromide and chloral hydrate, from barbiturates to benzodiazepines", to serotonergics, came to be used as well [1]. The Food and Drug Administration originally approved many gamma-aminobutyric acid (GABA) facilitating drugs since the 1960s for anxiety treatment. The 1980s evidenced the approval of a few serotonergic treatments that cornered the prescribing market and the front line of most treatment protocols. More recently, GABAergic drugs are making a return in the treatment of anxiety disorders. The following paper details the pharmacodynamic history of treating anxiety and also updates the reader as to the newer GABA-based approaches mentioned above.

Differences in total medical costs across the SSRIs for the treatment of depression and anxiety.

There is growing evidence that adherence to the recommended duration of antidepressant therapy results in reduced medical costs compared with nonadherence, and that the likelihood of adhering to therapy is not equivalent across the selective serotonin reuptake inhibitors (SSRIs). As such, the purpose of this study was to assess differences in 6-month medical costs between paroxetine controlled-release (CR) and immediate-release (IR) SSRI agents in a retrospective analysis of patients initiating SSRI therapy identified from the Integrated Healthcare Information Services National Managed Care Benchmark Database during a 2.5-year time frame. Inferential analyses were performed to evaluate differences in 6-month medical costs, controlling for differences in age, sex, utilization of psychiatric specialty care services, titration, pre-period costs, and comorbidity measures. Of the 146 075 patients included in this study, approximately 7% received paroxetine CR. Approximately 29.5% of patients had an anxiety disorder diagnosis; 26.0% had a depression-only diagnosis; and 13.2% had comorbid anxiety and depression. The 6-month medical costs were 244 US dollars lower for patients initiating with paroxetine CR compared with the average medical costs for patients receiving IR SSRIs. Paroxetine CR also had the lowest medical costs compared with each individual SSRI evaluated. After log transformation of costs and adjustment for baseline covariates, the aggregated IR SSRIs were associated with 8.7% higher 6-month medical costs than paroxetine CR (P <.001) and even greater costs after stratifying by diagnosis: 12.5% higher costs in patients with anxiety, 14.3% higher costs in patients with depression, and 15.9% higher costs in patients with comorbid anxiety and depression (P <.001 for all). Each individual IR SSRI was also associated with significantly higher medical costs than paroxetine CR, irrespective of diagnosis. As demonstrated, medical costs over a 6-month time frame were significantly greater for IR SSRIs versus paroxetine CR, even after adjusting for background characteristics and stratifying by diagnosis. Future studies should measure rates of adherence in relation to medical outcomes over an expanded time frame.

Implications of an SSRI generic step therapy pharmacy benefit design: an economic model in anxiety disorders.

As the antidepressant market continues to expand, it is important for healthcare decision makers to develop clinically and economically sound drug benefit designs. As such, the purpose of this study was to determine the economic implications of a generic step therapy (GST) formulary compared with an open formulary for selective serotonin reuptake inhibitors (SSRIs) in patients with anxiety disorders. A model simulating the SSRI treatment patterns of patients diagnosed with an anxiety disorder in a hypothetical health plan with 1 million members was developed. Treatment options were generic SSRI agents (ie, fluoxetine, paroxetine immediate release, and citalopram) and branded SSRI agents (ie, sertraline, paroxetine controlled release, and escitalopram). After treatment initiation, patients could achieve 180 days or more of continuous therapy with no evidence of therapy change, achieve less than 180 days of therapy with no evidence of therapy change, or have a change in therapy. Consequently, patients incurred differential average annual medical and prescription costs. Model probabilities and costs were estimated from published literature and database analyses. The GST formulary resulted in a greater frequency of therapy change than the open formulary (41.3% vs 36.8%) and a lower frequency of continuous therapy for at least 6 months (25.3% vs 29.8%). Costs of SSRI medication were lower for the GST formulary than for the open formulary (11.6 million US dollars vs 14.8 million US dollars ). Medical costs were considerably greater for the GST formulary than for the open formulary, however (178.7 US dollars million vs 174.9 million US dollars, respectively), with a total cost of 190.3 US dollars million for the GST formulary versus 189.6 US dollars million for the open formulary. The incremental cost of implementing a GST formulary over 1 year was 684 360 US dollars , or 0.06 US dollars per member per month. A sensitivity analysis indicated that the model was most sensitive to changes in the cost of SSRI drug therapy and the average annual medical costs for patients with evidence of therapy change. The results of this model indicate that implementing a GST formulary for SSRIs in patients with anxiety disorders may be associated with an increased amount of therapy change and early treatment discontinuation, resulting in an overall cost increase to a health plan.

Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?

The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na(+), Ca(2+) and K(+) channels often leading to life-threatening arrhythmia. To overcome the toxicity of old generation of antidepressants and antipsychotics, selective serotonin reuptake inhibitor antidepressants (SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxin) and several new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) were introduced during the past decade. Although these new compounds are not more effective in treating psychiatric disorders than older medications, they gained incredible popularity since they have been reported to have fewer and more benign side effect profile (including cardiovascular) than predecessors. Surprisingly, an increasing number of case reports have demonstrated that the use of SSRIs and new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) is associated with cases of arrhythmias, prolonged QTc interval on electrocardiogram (ECG) and orthostatic hypotension in patients lacking cardiovascular disorders, raising new concerns about the putative cardiovascular safety of these compounds. In agreement with these clinical reports these new compounds indeed show marked cardiovascular depressant effects in different mammalian and human cardiovascular preparations by inhibiting cardiac and vascular Na(+), Ca(2+) and K(+) channels. Taken together, these results suggest that the new generation of antidepressants and antipsychotics also have clinically important cardiac as well as vascular effects. Clinicians should be more vigilant about these potential adverse reactions and ECG control may be suggested during therapy, especially in patients with cardiovascular disorders. The primary goal of this review is to shed light on the recently observed clinically important cardiovascular effects of new antidepressants and antipsychotics and discuss the mechanism beyond this phenomenon.

Serotonergic antidepressants are associated with REM sleep without atonia.

STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is generally observed in older men and in individuals with specific neurologic diseases. There are case reports of RBD in individuals taking serotonergic antidepressants. Our objective was to assess electromyogram (EMG) activity during REM sleep in individuals taking serotonergic antidepressants and in a matched control group not on such medication. DESIGN: Chart review of clinical and polysomnographic data. SETTING: Sleep laboratory affiliated with a general hospital. PARTICIPANTS: 15 subjects taking a serotonergic antidepressant and 15 age-matched individuals not on such medication. MEASUREMENTS: Submental and anterior tibialis tonic and phasic EMG activity during REM sleep, REM latency, time in REM, apnea-hypopnea index, periodic leg movements of sleep index, and sleep-architecture measures. RESULTS: Tonic, but not phasic, submental EMG activity during REM sleep was significantly more common in the antidepressant-treated group than in the control group (P < .02). Tonic REM submental EMG activity correlated with REM latency (r = .42, P = .02) and inversely with REM time (r = -.36, P = .05). Subject age correlated with tonic REM submental EMG activity (r = .58, P = .02) in the antidepressant group There were also trends for more phasic activity in the anterior tibialis (P = .09) and submental (P = .07) EMG in REM sleep in the antidepressant group than in the control group. CONCLUSIONS: Subjects taking serotonergic antidepressants had more EMG activity in the submental lead during REM sleep than did controls. This correlated with measures of REM suppression and age. Individuals taking such medications may be at increased risk of developing REM sleep behavior disorder, particularly with increasing age.

Treating depression with selective serotonin reuptake inhibitors: a practical approach.

Depression is a common disorder that is becoming better understood as an illness that can be chronic, recurrent, and refractory to treatment. Depression can produce substantial suffering and profoundly affect a patient's self-esteem, relationships, and functional capacity. The improved adverse-effect profile and safety from overdose of selective serotonin reuptake inhibitors (SSRIs) have led to treatment of milder forms of depression and thus increased treatment of depression overall. This article synthesizes several previously published reviews and psychopharmacology resources and addresses practical issues related to initiating, monitoring, continuing, and discontinuing SSRIs. Precautions related to SSRI use and important considerations for various types of depression are discussed.

Role of pharmacogenomics in individualising treatment with SSRIs.

The introduction of the SSRIs has significantly transformed the pharmacological treatment of a range of psychiatric disorders. In particular, individuals affected by depression, panic disorder, obsessive-compulsive disorder and social phobia have benefited substantially from their use. Compared with the previous generation of psychotropic drugs, SSRIs offer an improved tolerability to therapy while maintaining a high level of efficacy. Nevertheless, despite these advantages, not all patients benefit from treatment; an appreciable proportion do not respond adequately, while others may react adversely. This necessitates a review of the initial treatment choice, often involving extended periods of illness while a more suitable therapy is sought. Such a scenario could be avoided were it possible to determine the most suitable drug prior to treatment. Several factors are postulated to influence outcome of drug therapy; most recently, pharmacogenetic studies have demonstrated a significant influence of genetic mechanisms on the efficacy of clinically prescribed drugs. This contribution, which is primarily a reflection of alterations in genes that encode drug-metabolising enzymes, drug receptors, transporters and second messengers, may be pertinent to the success of SSRI therapy. Attesting to this potential, studies to elucidate the influence of genetic processes on SSRI efficacy now represent a major focus of pharmacogenetics research. Current evidence emerging from the field suggests that gene variants within the serotonin transporter and cytochrome P450 drug-metabolising enzymes may bear a particular importance, though further corroboration of these findings is still warranted. At the same time, it appears likely that further key participating genes remain to be identified. By comprehensively delineating these genetic components, it is envisaged that this will eventually facilitate the development of highly sensitive protocols for individualising SSRI treatment.

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.

Transcultural issues in mood and anxiety disorders: a focus on Japan.

Accurate comparisons of the prevalence of psychiatric disorders across Eastern and Western cultures are difficult and limited by methodological problems. Nevertheless, using standardized diagnostic and evaluation techniques, recent surveys have suggested that depression and anxiety disorders exist in all countries and cultures examined thus far, although variations in the prevalence rates and symptomatology may exist. This article discusses the influence and impact that culture can have on recognizing and treating mood and anxiety disorders, with a particular focus on Japan. Over the last 20 years, studies have consistently reported an increase in mental illness in Japan, especially symptoms of depression and anxiety. While such symptoms have had an adaptive cultural role in the past, current social and economic changes in Japan have turned any adaptive advantage into a potentially significant disadvantage, with a major impact on the capacity of individuals to function adequately. The situation is compounded by the fact that Japanese patients are reluctant to openly discuss disturbances of mood, since these are considered to be indicative of personal weakness rather than treatable medical conditions. Reluctance to discuss personal mental health hinders timely recognition and appropriate treatment.

Pharmacologic differences among the SSRIs: focus on monoamine transporters and the HPA axis.

Depression is a widespread and serious disorder that afflicts an estimated 13.1 to 14.2 million adults in the United States each year. Even more compellingly, the lifetime prevalence rate of depression in the US has recently been estimated to include 16.2% of adults (21% women, 13% men), or >32.6 million people. There are multiple putative "causes" of depression, with approximately one-third of an individual's propensity for unipolar depression due to genetic vulnerability, while the remaining two-thirds is due to environmental factors. Although the selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to mainly act by selectively binding to the serotonin (5-HT) transporter to block reuptake of 5-HT from the synapse into the presynaptic nerve terminal, thereby increasing synaptic serotonin concentrations, some of the SSRIs also exhibit other neuropharmacologic effects. One such example is the high affinity for paroxetine in blocking norepinephrine reuptake. Another is the inhibition of dopamine reuptake by sertraline. In depression, hyperactivity of corticotropin-releasing factor (CRF)--producing neurons contribute to the well-characterized hypothalamic-pituitary-adrenal axis hyperactivity of depression. Increased activity of extrahypothalamic CRF circuits are believed to contribute to several depressive symptoms. Treatment and certain SSRIs have been shown to reduce the activity of CRF neurons and may contribute to their therapeutic action. Each SSRI apparently has its own unique pharmacologic properties that likely underlie their observed differences in clinical use.

Obsessive compulsive disorder: serotonin and beyond.

OCD was considered a rare, treatment refractory disorder of psychological origin, up until 20 years ago. Research in the last two decades has altered the perspectives regarding OCD. It is now clear that OCD is a prevalent disorder--about 2% of the population suffer from OCD--and that it is amenable both to psychological (cognitive-behavioural approach) and pharmacological intervention (with serotonergic medication). The biochemical and neuroanatomical (the frontal basal-thalamo cortical circuit) pathophysiology of OCD is also beginning to emerge. OCD is unique with regards to its specific response to serotonergic medication that blocks reuptake. Clomiprimine, fluoxetine, fluvoxemine, paroxetine, sertraline and citalopram were all found to be effective treatments for OCD based on large, multicentre, double-blind, placebo-controlled studies. As only serotonergic medications appear to be effective in OCD, the serotonergic hypothesis has been formulated and tested. Indeed, pharmacological challenges with specific serotonin agonists such as mCPP and sumatriptan, which were associated with transient exacerbation of OCD symptoms, are in line with the specific role of 5HT in the pathogenesis of OCD. However, this serotonergic hypothesis, while necessary, is not sufficient. It is clear that the dopaminergic and autoimmune mechanism are also implicated in the pathogenesis of OCD. Further studies are required to understand the relevance of the serotonergic and non-serotonergic systems in OCD, and to highlight the various possible subtypes of this intriguing disorder.

The new antidepressants. Selective serotonin reuptake inhibitors.

This article provides a resource for choosing among available SSRIs to treat pediatric patients. SSRIs are addressed according to five areas of interest: treatment efficacy data, untoward effects profile, pharmacokinetic characteristics, potential drug-drug interactions, and cost. Strategies for SSRI dosing and pretreatment work-up are also discussed. Included in the article is a reference table for SSRI dosing, available preparations, and cost per dose. Also included is an abbreviated reference table of important cytochrome P-450 isoenzymes, isoenzyme inhibition by SSRIs, and selected psychotropic and somatic medication substrates.