The impact of treatment with selective serotonin reuptake inhibitors on primate cardiovascular disease,behavior, and neuroanatomy

Selective serotonin reuptake inhibitor (SSRI) use is ubiquitous because they are widely prescribed for a number of disorders in addition to depression. Depression increases the risk of coronary heart disease (CHD). Hence, treating depression with SSRIs could reduce CHD risk. However, the effects of long term antidepressant treatment on CHD risk, as well as other aspects of health, remain poorly understood. Thus, we undertook an investigation of multisystem effects of SSRI treatment with a physiologically relevant dose in middle-aged adult female cynomolgus monkeys, a primate species shown to be a useful model of both depression and coronary and carotid artery atherosclerosis. Sertraline had no effect on depressive behavior, reduced anxious behavior, increased affiliation, reduced aggression, changed serotonin neurotransmission and volumes of neural areas critical to mood disorders, and exacerbated coronary and carotid atherosclerosis. These data suggest that a conservative approach to prescribing SSRIs for cardiovascular or other disorders for long periods may be warranted, and that further study is critical given the widespread use of these medications.     

Brief Report: Aggression and Stereotypic Behavior in Males with Fragile X Syndrome—Moderating Secondary Genes in a “Single Gene” Disorder

Although fragile X syndrome (FXS) is a single gene disorder with a well-described phenotype, it is not known why some individuals develop more significant maladaptive behaviors such as aggression or autistic symptoms. Here, we studied two candidate genes known to affect mood and aggression, the serotonin transporter (5-HTTLPR) and monoamine oxidase A (MAOA-VNTR) polymorphisms, in 50 males with FXS ages 8–24 years. Mothers and fathers of participants reported the frequency and severity of aggressive/destructive, self-injurious, and stereotypic behaviors. Polymorphism genotypes were unrelated to age and IQ. Results showed a significant effect of 5-HTTLPR genotype on aggressive/destructive and stereotypic behavior; males with FXS who were homozygous for the high-transcribing long (L/L) genotype had the most aggressive and destructive behavior, and individuals homozygous for the short (S/S) genotype had the least aggression. Those with the L/L genotype also had the highest levels of stereotypic behavior. There was no effect of MAOA-VNTR on behavior; however those with the high-activity, 4-repeat genotype were more likely to be taking SSRI or SNRI medication. This preliminary study prompts consideration of secondary genes that may modify behavioral phenotype expression in neurodevelopmental disorders, even those with a single gene etiology such as FXS.     

Efficacy of atypical antipsychotics in depressive syndromes

Depression is a frequent symptom in psychiatry, either isolated (major depression) or entangled with other psychiatric symptoms (psychotic depression, depression of bipolar disorders). Many antidepressant drugs are available with different pharmacological profiles from different classes: tricyclic antidepressants, monoamine oxydase inhibitors, selective serotonin reuptake inhibitors (SSRI). However, there are some limitations with these drugs because there is a long delay before relief for symptoms, some patients with major depression are resistant to treatment, there is a risk to induce manic symptoms in patients with bipolar disorders and these drugs have no effect on the psychotic symptoms frequently associated to major depression. The leading hypothesis for the search of more efficient new antidepressants has been the amine deficit hypothesis: noradrenaline and/or serotonin deficit and more recently dopamine deficit. Moreover, a dopamine deficit has been also hypothesized as the central mechanism explaining the negative symptoms of schizophrenia. These symptoms are the consequence of a deficit of normal behaviours and include affective flattening, alogia, apathy, avolition and social withdrawal. There is thus a great overlap between symptoms of depression and negative symptoms of schizophrenia. Atypical antipsychotics, in contrast with conventional neuroleptics, have been shown to decrease negative symptoms, most probably through the release of dopamine in prefrontal cortex, thus improving psychomotor activity, motivation, pleasure, appetite, etc. The dopamine deficit in cortical prefrontal areas was thus an unifying hypothesis to explain both some symptoms of depression and negative symptoms of schizophrenia. Studies in animal confirm this view and show that the association of an atypical antipsychotic drug and an SSRI (olanzapine plus fluoxetine) increases synergistically the release of dopamine in prefrontal areas. Moreover, most of the atypical antipsychotics have a large action spectrum, beyond the only dopamine receptors: their effects on the serotonin receptors--particularly the 5-HT2A and 5-HT2C receptors--suggest that their association to SSRI could be a promising treatment for depression. Indeed, SSRI act mainly by increasing the serotonin level in the synapse, thus leading to a non specific activation of all pre- and post-synaptic serotonin receptors. Among them, 5-HT2A/2C receptors have been involved in some of the unwanted effects of SSRI: agitation, anxiety, insomnia, sexual disorders, etc. The inhibition of these receptors could be thus beneficial for patients treated with SSRI. Amisulpride is an unique atypical antipsychotic that selectively blocks dopamine receptors presynaptically in the frontal cortex, possibly enhancing dopaminergic transmission. The antidepressant effect of amisulpride was shown in dysthymia in many clinical studies versus placebo, tricyclic antidepressants, SSRI or others. However, a shorter delay for symptom relief was not demonstrated for amisulpride as compared to comparative antidepressants. Other atypical antipsychotics (clozapine, olanzapine), which act on a large variety of receptors, have shown antidepressant effects--mainly in association with SSRI--in different psychiatric diseases: treatment-resistant major depression, major depression with psychotic symptoms and depression of bipolar disorders, with no increase of manic symptoms in this latter case. Moreover, the delay for symptom relief was greatly shortened. More comparative double-blind studies are required to confirm and to precise the antidepressant effects of atypical antipsychotics. Nevertheless, these studies suggest that atypical anti-psychotics could be of great value in depressive conditions reputed for their resistance to treatment with usual antidepressants. Particularly, new strategies emerge that combine atypical antipsychotics and antidepressants for greater efficacy and more rapid relief of depression symptoms.     

A systematic chart review of the nature of psychiatric adverse events in children and adolescents treated with selective serotonin reuptake inhibitors

OBJECTIVE: Despite a rapidly growing literature on the efficacy of the selective serotonin reuptake inhibitors (SSRI) in the treatment of juvenile psychiatric disorders, relatively little is described about emotional, behavioral, and cognitive adverse effects associated with their use. To this end we completed a retrospective analysis of medical charts to determine the incidence, nature, and clinical correlates of treatment emergent adverse effects in the behavioral, cognitive, and emotional domains. METHODS: We systematically evaluated the medical charts of children treated with SSRI for depressive or obsessive-compulsive disorders for a mean (+/- SD) of 26.9 + 20.8 months to determine the incidence, nature, and clinical correlates of treatment emergent psychiatric adverse events (PAE). Charts were reviewed for diagnoses, type and dose of SSRI and adjunct medication, specific type of PAE, and time to onset and offset of PAE. RESULTS: In total, 82 charts of children and adolescents (mean age 12.2 +/- 3.2 years) were examined. PAE occurred in 22% of children and were most commonly related to disturbances in mood. PAE were not associated with psychiatric diagnosis(es), age, sex, concurrent medications, doses or specific serotonin reuptake inhibitors. The onset of PAE was observed typically 3 months after SSRI exposure (median = 91 days). Although PAE diminished with SSRI discontinuation, those that emerged early in treatment diminished significantly more rapidly than those that emerged later (median offset was 10 and 49 days, respectively). Re-exposure to an SSRI resulted in another PAE in 44% (n = 18) of the group. CONCLUSION: Based on the retrospective review of medical charts, youth receiving SSRI appear to be at risk for treatment emergent PAE and recurrence with re-exposure to an SSRI. Prospective longer term studies evaluating the course and prognosis of youths manifesting PAE to SSRI are necessary.     

Tolerability of selective serotonin reuptake inhibitors in thirty-nine children under age seven: a retrospective chart review

OBJECTIVE: To characterize the adverse effects of treatment with selective serotonin reuptake inhibitors (SSRIs) started in children under age 7 yr. METHODS: We conducted a retrospective review of medical records for all children who had begun treatment with an SSRI under age 7 at an academic psychiatry department in Boston. RESULTS: Thirty-nine children (26 males, 13 females) met the inclusion criteria. Mean age at start of treatment was 5.9 +/- 0.8 yr, and median treatment duration was 5.0 months. The target diagnoses for SSRI treatment were anxiety disorders in 54%, depressive disorders in 23%, and both anxiety and depressive disorders in 20% of patients. There were no reports of suicidal ideation or attempt. No children were medically or psychiatrically hospitalized for adverse effects (AEs). Eleven patients (28%) reported an AE of at least moderate severity; 7 (18%) discontinued the SSRI due to the AE. Six patients discontinued due to behavioral activation and 1 due to gastrointestinal upset. The median time to onset of an AE was 23 days, and median resolution was 19 days from onset. CONCLUSIONS: The high rate of adverse effects, especially activation, in this sample argues for continued caution in using SSRIs in young children. Controlled trials are warranted.     

Interleukin-1beta Causes Fluoxetine Resistance in an Animal Model of Epilepsy-Associated Depression

Depression represents a common comorbidity of epilepsy and is frequently resistant to selective serotonin reuptake inhibitors (SSRI). We tested the hypothesis that the SSRI resistance in epilepsy associated depression may be a result of a pathologically enhanced interleukin-1β (IL1-β) signaling, and consequently that the blockade of IL1-β may restore the effectiveness of SSRI. Epilepsy and concurrent depression-like impairments were induced in Wistar rats by pilocarpine status epilepticus (SE). The effects of the 2-week long treatment with fluoxetine, interleukin-1 receptor antagonist (IL-1ra), and their combination were examined using behavioral, biochemical, neuroendocrine, and autoradiographic assays. In post-SE rats, depression-like impairments included behavioral deficits indicative of hopelessness and anhedonia; the hyperactivity of the hypothalamo-pituitary-adrenocortical axis; the diminished serotonin output from raphe nucleus; and the upregulation of presynaptic serotonin 1-A (5-HT1A) receptors. Fluoxetine monotherapy exerted no antidepressant effects, whereas the treatment with IL-1ra led to the complete reversal of anhedonia and to a partial improvement of all other depressive impairments. Combined administration of fluoxetine and IL-1ra completely abolished all hallmarks of epilepsy-associated depressive abnormalities, with the exception of the hyperactivity of the hypothalamo-pituitary-adrenocortical axis, the latter remaining only partially improved. We propose that in certain forms of depression, including but not limited to depression associated with epilepsy, the resistance to SSRI may be driven by the pathologically enhanced interleukin-1β signaling and by the subsequent upregulation of presynaptic 5-HT1A receptors. In such forms of depression, the use of interleukin-1β blockers in conjunction with SSRI may represent an effective therapeutic approach.     

Relationship between antidepressants and suicide attempts: an analysis of the Veterans Health Administration data sets

OBJECTIVE: In late 2006, a U.S. Food and Drug Administration advisory committee recommended that the 2004 black box warning regarding suicidality in pediatric patients receiving antidepressants be extended to include young adults. This study examined the relationship between antidepressant treatment and suicide attempts in adult patients in the Veterans Administration health care system. METHOD: The authors analyzed data on 226,866 veterans who received a diagnosis of depression in 2003 or 2004, had at least 6 months of follow-up, and had no history of depression from 2000 to 2002. Suicide attempt rates overall as well as before and after initiation of antidepressant therapy were compared for patients who received selective serotonin reuptake inhibitors (SSRIs), new-generation non-serotonergic-specific (non-SSRI) antidepressants (bupropion, mirtazapine, nefazodone, and venlafaxine), tricyclic antidepressants, or no antidepressant. Age group analyses were also performed. RESULTS: Suicide attempt rates were lower among patients who were treated with antidepressants than among those who were not, with a statistically significant odds ratio for SSRIs and tricyclics. For SSRIs versus no antidepressant, this effect was significant in all adult age groups. Suicide attempt rates were also higher prior to treatment than after the start of treatment, with a significant relative risk for SSRIs and for non-SSRIs. For SSRIs, this effect was seen in all adult age groups and was significant in all but the 18-25 group. CONCLUSIONS: These findings suggest that SSRI treatment has a protective effect in all adult age groups. They do not support the hypothesis that SSRI treatment places patients at greater risk of suicide.     

Serotoninwiederaufnahmehemmer im Kindes- und Jugendalter

Recent reports and recommendations from national and international health care regulatory authorities have informed us that serotonin reuptake inhibitors (SSRI) are contraindicated as new treatment for those under 18 years of age with depressive illness. They conclude that SSRI carry the risk of increased suicide-related behavior; although there was no completed suicide. The European Medicine Agency (EMEA) and German regulatory agency (BfArM) advise that these components generally should not be used in this age group except in their other, approved indications. However, it is acknowledged that they may sometimes be chosen, depending on individual clinical needs. Based on these data, the Commission for Child and Adolescent Developmental Psychopharmacology of the German Scientific Society for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy is trying to give recommendations for the use of SSRI in clinical practice. Recent studies demonstrate that combining SSRI with psychological treatment such as cognitive behavioral therapy may reduce the risk of suicidal behavior in depressed children and adolescents.     

Treatment-emergent mania/hypomania in unipolar patients

Objective:  The aim of this study was to estimate the incidence of treatment-emergent mania/hypomania (TEMH) and to describe the clinical characteristics of patients with major depression experiencing this event during treatment with a selective serotonin reuptake inhibitor (SSRI) and/or interpersonal psychotherapy (IPT).
Methods:  Following an algorithm-based protocol, 344 patients with major depression confirmed with the Structured Clinical Interview for DSM-IV disorders were treated with an SSRI, interpersonal psychotherapy, or their combination for nine months. The emergence of mania/hypomania was carefully monitored throughout the study using the Young Mania Rating Scale and clinical assessment.
Results:  Overall, eight patients experienced TEMH. The incidence of this event was 3.0% in patients treated with an SSRI and 0.9% in patients treated with IPT alone. Among patients treated with an SSRI, the difference between sites was higher than expected by chance alone (6.8% at Pisa and 0% at Pittsburgh, p = 0.002). Despite the adoption of an identical protocol at the two sites, some demographic and clinical characteristics of participants may account for this unexpected result. Alternatively, the greater number of episodes and earlier age of onset at the Pittsburgh site suggests that the unipolar course of illness was more clearly established prior to study entry.
Conclusions:  TEMH is an infrequent event, occurring in 2.3% of patients treated for major depression. Nevertheless, its consequences are clinically relevant and require prompt and appropriate therapeutic interventions. For this reason, recognising those patients at risk for such an event is of paramount clinical significance. The observed difference in the incidence of TEMH between the two sites requires further investigation.     

Inositol addition does not improve depression in SSRI treatment failures

Summary. Some antidepressants, such as Lithium, can augment the antidepressant effect of serotonin selective uptake inhibitors (SSRI) in patients who have failed to respond to SSRI. Inositol has demonstrated antidepressant effects but in a controlled double blind augmentation trial did not improve depression in SSRI treatment failures. Received January 22, 1999; accepted April 7, 1999     

Clinical features of patients with obsessive-compulsive disorder showing different pharmacological responses]

BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharmacological treatment for obsessive-compulsive disorder (OCD), some OCD patients do not show improvement. Sometimes, the addition of a low-dose atypical antipsychotic, such as risperidone, or olanzapine, to ongoing SSRI treatment has been shown to be effective. However, there are patients who still show no response after trials with this augmentation therapy. In the present study, we examined the clinical features of OCD patients who showed different responses to pharmacological treatment. SUBJECTS AND METHOD: Fifty OCD patients were divided into three groups according to their pharmacological responses: responders to SSRI (group A: n= 25), responders to SSRI with an atypical antipsychotic (group B: n= 15), and non-responders to both SSRI and SSRI with an atypical antipsychotic (group C: n= 10). We examined the clinical features such as age, sex, age of onset, duration of illness, types of obsessive-compulsive symptoms, severity, improvement after treatment, insight into disease, depression, comorbidity, involving family members in compulsive or ritualistic behavior, and the level of social adaptation of each OCD group. RESULTS: Twenty five patients showed a good response to SSRI monotherapy, 15 showed a response to antipsychotic augmentation, and 10 were non-responders to both SSRI and SSRI with an atypical antipsychotic. Significantly lower insight levels were observed only in group B and higher depressive levels in group C. OCD patients who were refractory to SSRI monotherapy showed comorbidity at a significantly higher frequency. OCD patients in group A showed significantly greater improvement, and group B showed inferior social adaptation after treatment. There were no significant differences in age, sex, age of onset, duration of illness, severity, involving family members in compulsive or ritualistic behavior, and social adaptation before treatment in the three OCD groups. CONCLUSION: There were differences in the clinical features of OCD patients who showed different responses to pharmacological treatment. Our results suggest that OCD is clinically and biologically heterogeneous. It may be important to divide OCD patients into subgroups for future studies.     

Treatment-emergent suicidal ideation during 4 months of acute management of unipolar major depression with SSRI pharmacotherapy or interpersonal psychotherapy in a randomized clinical trial

Background: To date, few randomized controlled trials (RCTs) of major depression have examined suicidal ideation as an outcome measure. Our aim is to determine the incidence of treatment‐emergent suicidal ideation (ESI) and behaviors during the acute phase of treatment with an SSRI antidepressant or interpersonal psychotherapy (IPT) in patients with unipolar major depression. Methods: In a two‐site RCT, 291 adult outpatients with nonpsychotic major depression and a Hamilton Depression Rating Scale (HDRS) score ≥15 were randomly allocated to IPT or SSRI. Participants who did not remit with monotherapy received augmentation with the other treatment. ESI was defined as a postbaseline HDRS suicidality item score ≥2 or a postbaseline Quick Inventory of Depressive Symptomatology (QIDS) score ≥2 in patients with a baseline score ≤1. Results: Of the 231 participants who had no suicidal ideation at baseline, 32 (13.8%) subsequently exhibited ESI on at least one postbaseline visit. Time to suicidal ideation was significantly longer in patients allocated to SSRI compared to those allocated to IPT (HR = 2.21, 95% CI 1.04–4.66, P = .038), even after controlling for treatment augmentation, benzodiazepine use, and comorbidity with anxiety disorders. Worsening of suicidal ideation occurred in 7/60 patients who had suicidal ideation at baseline. In the large majority of cases, suicidal ideation was successfully managed with the study protocol. Conclusions: In the context of careful monitoring and frequent contact, selective serotonin reuptake inhibitor (SSRI) was associated with a lower risk of ESI than IPT and both SSRI and IPT appeared to be safe treatments for patients with past suicide attempts, none of whom exhibited ESI during the study. Depression and Anxiety, 2011.© 2011 Wiley‐Liss, Inc.     

An emerging role for escitalopram in the treatment of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a common and severe neuropsychiatric disorder treated by both behavioral and pharmacologic techniques. Despite the availability of treatments for OCD, including the selective serotonin reuptake inhibitors (SSRIs), many OCD patients have an inadequate response to current treatments. As such, additional approaches to the management of OCD are required. A potential but little studied treatment for OCD is the SSRI escitalopram. Escitalopram is the S-enantiomer of citalopram, the preparation containing both S and R enantiomers of citalopram. Not only is escitalopram the most selective of the SSRIs, it is also devoid of R-citalopram, which may interfere with the effects of the S enantiomer. Escitalopram appears to be effective in depression and several anxiety disorders, including social anxiety disorder and generalized anxiety disorder, conditions in which it also appears reasonably well tolerated. Enantiomeric specificity, high serotonin reuptake selectivity, comparatively good tolerability and favorable pharmacokinetics, and preliminary evidence of efficacy in OCD suggest a potential role for the use of escitalopram in the treatment of OCD. Nevertheless, additional work including evaluating the use of escitalopram with behavioral interventions and in long-term treatment of OCD is needed to clarify its overall role in managing OCD.     

Hyponatraemia in elderly psychiatric patients treated with Selective Serotonin Reuptake Inhibitors and venlafaxine: a retrospective controlled study in an inpatient unit

OBJECTIVE: To determine the prevalence of hyponatraemia associated with selective serotonin reuptake inhibitor (SSRI) and venlafaxine use in elderly patients compared to that in elderly patients not prescribed these drugs, while controlling for age, sex, depression status and illnesses or prescribed medications also associated with hyponatraemia. Design and setting Retrospective controlled analysis in a 36-bed inpatient unit for elderly psychiatric patients in Melbourne. PATIENTS: Inpatients (199) with a mean age of 74.2 years of whom 74 were prescribed an SSRI or venlafaxine. RESULTS: Patients on SSRIs or venlafaxine were 5.6 times as likely as patients not so treated to have hyponatraemia. Thirty-nine percent of patients on an SSRI or venlafaxine had hyponatraemia compared with 10% of controls. Ten of the 14 patients on venlafaxine were hyponatraemic. Controlling for thiazide status did not reduce the odds of these patients having hyponatraemia and taking an SSRI or venlafaxine was still strongly associated with hyponatraemia after also controlling for age, sex, and depression status, consumption of other drugs potentially causative of hyponatraemia and medical illness severity (Odds Ratio (OR) 3.5, p = 0.008). CONCLUSIONS: SSRI and venlafaxine use is strongly associated with the presence of hyponatraemia in a population of elderly psychiatric inpatients and the association is not due to confounding by age, sex, depression status, medical illness severity or consumption of other drugs. Elderly patients on SSRIs or venlfaxine should have sodium levels checked before and after commencement of antidepressant treatment.     

Emergence of depressive symptoms during treatment for panic disorder with specific 5-hydroxytryptophan reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRI) have been established as effective drugs in the treatment of depressive and anxiety disorders. However, there are also reports that they can induce depressive symptoms and suicidal thoughts in patients. Eighty of 230 patients who met the DSM-III-R criteria for panic disorder received, during the course of treatment, fluvoxamine (a selective serotonin reuptake inhibitor) at a dose level between 50–200 mg/day. The patients were clinically evaluated for a history of affective disorder and for the presence of affective symptoms before the treatment and for emergence of depressive symptoms during the treatment. Seven of the 80 patients (9%) developed symptoms of depression despite a good antianxiety response. Five of the 7 patients received fluvoxamine as second choice after tricyclic antidepressants (TCA). These patients had no history of affective disorder, and no symptoms of depression were present before the treatment with fluvoxamine. The depressive symptoms abated after the fluvoxamine was discontinued and TCA or clonazepam was prescribed. The depressive symptoms reappeared when fluoxetine was administered. None of these 7 patients developed depressive symptoms while treated with TCA or clonazepam. Among the 150 patients treated with TCA and benzodiazepines, not a single case of depression was seen in patients without a previous history of depression. These results suggest a vulnerability among some of panic disorder patients to noradrenergic-serotonergic imbalance caused by SSRI, which has to be taken into clinical consideration.     

Escitalopram: A New SSRI for the Treatment of Depression in Primary Care

Escitalopram is the S-enantiomer of the racemic compound citalopram, a selective serotonin reuptake inhibitor (SSRI) widely used for the treatment of depression. This review describes the current body of pharmacologic and clinical evidence supporting the use of escitalopram for the treatment of depression and anxiety. Preclinical studies have confirmed that it is primarily this molecule that provides the inhibition of serotonin reuptake responsible for the antidepressant effect of citalopram, with minimal-to-nonexistent affinity for other receptor sites. Clinical trials of escitalopram in depressed patients indicate that escitalopram, 10 mg/day, is as effective as 40 mg/day of its parent compound, citalopram, with an excellent safety and tolerability profile. Because of its increased selectivity, escitalopram represents a refinement in SSRI therapy for symptoms of depression and anxiety. This article also explores the implications of a more selective SSRI on the management of depressed patients in the primary care clinical practice.     

不同类型抗抑郁剂在双相抑郁治疗中导致转相的回顾性研究

目的比较不同抗抑郁剂在双相抑郁治疗过程中转相率的差异。方法对150例接受抗抑郁剂治疗的双相抑郁患者出现躁狂、轻躁狂、快速循环情况进行调查，并比较不同抗抑郁剂之间的差异。结果150例双相抑郁中，共有41例患者在治疗过程中转相，总发生率（转相率）34％。其中使用双重作用抗抑郁剂（DAA）患者的转相率为29．2％，使用选择性5-羟色胺回吸收抑制剂〈SSRI）的患者为12.7％，DAA与SSRI联合应用者为48．7％，三组间差异有统计学意义（Χ^2=11．87，P〈0．001）。DDA与SSRI联合应用者转相率高于SSRI，差异有统计学意义（Χ^2=16．06，P〈0．001，危险比OR=6．53）；DAA转相率高于SSRI。差异有统计学意义（Χ^2=4.65，P〈0．01，OR=6．53）；DAA与SSRI联合应用者转相率高于DAA（Χ^2=3．49，P〉0.05，OR=2．31）。转相与未转相者相比，心境稳定剂的应用差异有统计学意义（7／41，52／109，Χ^2=11．72，P〈0．001）。结论不同类型抗抑郁荆在双相抑郁治疗中引起的转相率有差异，其中联合使用抗抑郁剂的转相率最高，而心境稳定剂的联合应用有助于预防转相。     

SSRI treatment of borderline personality disorder: a randomized,placebo-controlled clinical trial for female patients with borderline personality disorder

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are recommended for treatment of affect lability, impulsivity, and aggression in patients with borderline personality disorder. This recommendation is based on positive findings in at least 10 open studies and one small double-blind study of SSRIs for patients with borderline personality disorder and one study of impulsive aggressive patients with different personality disorders. A randomized, placebo-controlled SSRI study with borderline personality disorder patients, however, provided inconclusive results because of a large response to placebo. It was, therefore, decided to conduct a new randomized trial with a larger study group. METHOD: A double-blind, placebo-controlled, randomized trial using the SSRI fluvoxamine for 6 weeks followed by a blind half-crossover for 6 weeks and an open follow-up for another 12 weeks was conducted with 38 nonschizophrenic, nonbipolar female patients with borderline personality disorder. The outcome measures were the rapid mood shift, impulsivity, and aggression subscales from the Borderline Personality Disorder Severity Index. RESULTS: Fluvoxamine but not placebo produced a robust and long-lasting reduction in the scores on the subscale for rapid mood shifts. In contrast, no difference between the fluvoxamine and placebo groups was observed in the effect on the impulsivity and aggression scores. CONCLUSIONS: In this study, fluvoxamine significantly improved rapid mood shifts in female borderline patients, but not impulsivity and aggression. This latter finding may be due to gender-specific differences in impulsivity and aggression.