Nadolol to treat aggression and psychiatric symptomatology in chronic psychiatric inpatients: a double-blind, placebo-controlled study.

BACKGROUND: Considerable evidence indicates that the lipophilic beta-blocker propranolol is useful in treating organically based aggression. This study looked at the efficacy of a more hydrophilic beta-blocker, nadolol, to treat aggression in chronic psychiatric inpatients. METHOD: Forty-one chronic psychiatric inpatients with an average of one aggressive outburst per week (defined by the Overt Aggression Scale [OAS]) were entered into a double-blind, placebo-controlled study lasting 17 weeks. The OAS was used to track aggression on a per-incident basis, while the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions scale (CGI) were used to track clinical status. RESULTS: Nadolol subjects showed a significant decline in frequency of aggression compared with controls (p = .026) and a significant decline in the BPRS total score (p = .007) and in the subfactors "hostility and suspicion," "negative symptoms," and "signs of hyperarousal/tension." There was no significant change in CGI "severity of illness" ratings between groups, although the nadolol group was significantly improved from baseline at every subsequent time period while the placebo group was unchanged throughout the study. CONCLUSION: Nadolol is of significant benefit in the treatment of aggression in chronic psychiatric inpatients. This drug does penetrate the brain over time, but the success of a drug whose primary locus of action is peripheral may implicate a bimodal mechanism of action, i.e., a role for the CNS and the soma in the maintenance of aggression.     

Aggressive symptoms in children with tic disorders

Episodes of explosive anger and aggression are reported in patients with tic disorders and probably contribute to psychosocial stress and low quality of life. The source of these symptoms is controversial. The objective of the study was to study the relationship between tic disorders, their associated comorbidities, and aggressive behavior. The cohort included 47 children and adolescents (age 7–17 years) with Tourette syndrome or other chronic tic disorders attending a tertiary pediatric Tourette clinic. Associated psychopathology was assessed with the Yale Global Tic Severity Scale, Yale Brown Obsessive Compulsive Scale, Conners ADHD Rating Scale, Screen for Child Anxiety-Related Emotional Disorders, and Child Depression Inventory. Aggression was assessed with the Overt Aggression Scale and scores were compared with a group of 32 healthy age- and sex-matched children. There were no significant differences in aggression scores between the children with tic disorders and controls. Verbal aggression was the most prevalent type of aggression, found in 70% of the patients with tic disorders. The level of aggression was not correlated to tic severity. Comorbid attention-deficit hyperactivity disorder and obsessive–compulsive disorder increased the probability of aggressive behavior in patients with tic disorders. On regression analysis, the only significant predictor of aggression was the severity of attention-deficit hyperactivity disorder. This study suggests that there is no difference in aggressive behavior between children with tics without comorbidities and healthy children. It is possible that aggressive behavior in children with tic disorders is predominantly associated with comorbid attention-deficit hyperactivity disorder.

     

Olanzapine treatment in adolescents with severe conduct disorder.

The most severe forms of conduct disorder (CD) are highly stable and disabling disorders, more likely to persist in time and to evolve into disruptive or antisocial behaviors. One crucial issue in the prognosis of these forms of CD is the high resistance to both non-pharmacological and pharmacological treatments, with antipsychotic drugs being frequently used in refractory cases. Aim of this study was: (1) to explore efficacy and tolerability of olanzapine treatment in adolescents with severe CD; (2) to identify predictors of olanzapine treatment outcome. This was a retrospective study, based on clinical records of the first 23 adolescents diagnosed as having a CD, diagnosed with a clinical interview (K-SADS), either pure or with comorbid diagnoses, and treated with olanzapine. All these patients did not respond satisfactorily to non-pharmacological intervention and to adequate dosages of mood stabilizers (lithium and/or valproate). The sample consisted of 16 males and seven females, 16 inpatients and seven outpatients (mean age 13.6 +/- 1.9 years, range 11-17.2 years), followed-up for a period ranging from 6 to 12 months (mean 8.8 +/- 2.7 months). Outcome measures included the Modified Overt Aggression Scale (MOAS), Clinical Global Impression-Improvement (CGI-I) and Children Global Assessment Scale (CGAS). During the follow-up, all patients were involved in non-pharmacological treatments (psychotherapy, family therapy, or day-hospital group treatments). Based on both an improvement of at least 50% at MOAS and a score 1 or 2 at CGI-I, 14 out of 23 patients (60.9%) were classified as responders at the end of the follow-up. Significant improvement at the last observation was found in MOAS (P < 0.001) and CGAS (P < 0.001) scores. Olanzapine dosage was 8 +/- 3.2 mg/day (range 5-20 mg/day). Mean weight gain at the end of the follow-up was 4.6 +/- 3 kg. The predictors of a positive treatment response was an impulsive-affective versus controlled-predatory type of aggression. Age at onset of CD and comorbid disorders did not affect treatment response. These preliminary findings suggest that olanzapine may improve behavior in adolescents with severe and treatment-refractory CD and impulsive aggression.     

院前具有攻击行为的急性精神分裂症患者的住院治疗特点

目的 了解院前发生攻击行为的急性精神分裂症患者住院治疗的临床干预措施和治疗效果的特点.方法 以151例急性精神分裂症新入院患者为研究对象,采用自编一般情况调查表和疾病信息调查表收集疾病相关信息,应用修订版外显攻击行为量表(MOAS)、阳性和阴性症状量表的兴奋因子(PANSS-EC)、行为活动评定量表(BARS)、风险评估量表、临床总体印象量表(CGI)评估其精神病理症状、护理风险和治疗效果,根据MOAS评分将研究对象分为攻击行为患者组和无攻击行为患者组,进行组间比较.结果 (1)151例患者中,入院前一周内有攻击行为者74例,无攻击行为者77例.(2)相对于无攻击行为患者组,攻击行为患者组既往有暴力/攻击史者比例较高,入院前1周未服药比例较高;入院时疾病严重程度较重,PANSS-EC、BARS和MOAS评分均较高;攻击风险和防攻击护理医嘱率较高,差异均有统计学意义(P<0.05);(3)两组患者入院时医生处方口服药物均为新型抗精神病药物,利培酮使用比例为68.9%,其次为奥氮平(13.2%)、喹硫平(5.3%),组间差异无统计学意义(P>0.05);攻击行为患者组氟哌啶醇注射率和保护性约束使用率明显高于无攻击行为患者组(P<0.05);(4)出院时,两组患者疾病严重程度、PANSS-EC评分、MOAS评分和出院疗效组间差异均无统计学意义(P>0.05).结论 院前发生攻击行为的急性期精神分裂症患者相对于无攻击行为者,住院治疗疗效相当,但入院时病情较重,较为兴奋激越,攻击风险和出走风险较高,住院期间肌肉注射抗精神病药物和保护性约束等措施应用较多.     

A randomized controlled trial of risperidone in the treatment of aggression in hospitalized adolescents with subaverage cognitive abilities

BACKGROUND: Risperidone is an atypical antipsychotic drug that blocks dopamine as well as serotonin receptor systems. The present study was designed to examine the efficacy and safety of risperidone in a 6-week double-blind, randomized, parallel-group design in the treatment of aggression in adolescents with a primary diagnosis of DSM-IV disruptive behavior disorders and with subaverage intelligence. METHOD: We randomly assigned 38 adolescents (33 boys; 10 subjects with slightly subaverage IQ, 14 with borderline IQ, and 14 with mild mental retardation), who were hospitalized for treatment of psychiatric disorders associated with severe aggression, to receive risperidone or placebo. The main efficacy measures were the Clinical Global Impressions-Severity of Illness scale (CGI-S), the modified Overt Aggression Scale (OAS-M), and the Aberrant Behavior Checklist (ABC). Side effects were measured using the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS: The mean daily dose of risperidone at the end of treatment was 2.9 mg (range, 1.5-4 mg). Risperidone, compared with placebo, was associated with significant improvements on the CGI-S (p < .001) and the at-school ABC overall and hyperactivity scales (p < .05). During a 2-week washout following the 6-week trial, a statistically significant worsening was found in the risperidone group on the CGI-S scale, the OAS-M. and the ABC. Extrapyramidal symptoms were absent or very mild during risperidone treatment. Transient tiredness was present in 11 (58%) of 19 drug-treated subjects. Other untoward effects included sialorrhea, nausea, and slight weight gain (mean = 3.5% of body weight in the risperidone group). No clinically relevant changes were found in laboratory parameters, electrocardiogram, heart rate, or blood pressure. CONCLUSION: These results suggest that risperidone may be effective for severe aggression in adolescents with disruptive behavior disorders and subaverage intelligence, and these results are consistent with reports suggesting its effectiveness for treating severe aggression in adolescents in general.     

Impact of trait impulsivity and state aggression on divalproex versus placebo response in borderline personality disorder

OBJECTIVE: The authors' goal was to determine whether specific pretreatment clinical characteristics differentially predict favorable treatment response to divalproex versus placebo for impulsive aggression in patients with borderline personality disorder. METHOD: Fifty-two outpatients with DSM-IV borderline personality disorder were randomly assigned to receive divalproex (N=20) or placebo (N=32), double-blind, for 12 weeks. Trait impulsivity symptoms were determined by using the Barratt Impulsiveness Scale, and state aggression symptoms were determined by using the Overt Aggression Scale modified for outpatients. Affective stability was determined by using the Young Mania Rating Scale and the Hamilton Depression Rating Scale. Analyses were performed to identify possible baseline symptom domains that predict treatment response. RESULTS: Divalproex was superior to placebo in reducing impulsive aggression in patients with borderline personality disorder. Divalproex-treated patients responded better than placebo-treated patients among those with higher baseline trait impulsivity symptoms and state aggression symptoms. The effects of baseline trait impulsivity and state aggression appear to be independent of one another. However, baseline affective instability did not influence differential treatment response. CONCLUSIONS: Both pretreatment trait impulsivity symptoms and state aggression symptoms predict a favorable response to divalproex relative to placebo for impulsive aggression in patients with borderline personality disorder.     

Reboxetine as an optional treatment for hyperkinetic conduct disorder: a prospective open-label trial

BACKGROUND AND PURPOSE: Hyperkinetic conduct disorder (HCD) has been identified as a common psychiatric diagnosis among children and adolescents. This disorder affects many life aspects of both child and family. The aim of this study was to examine the efficacy of the selective norepinephrine reuptake inhibitor (SNRI), reboxetine, in treating children with HCD and its influence on associated symptoms, such as aggressiveness, impulsivity, anxiety, and depression. METHODS: Fifteen children, 5-14 years of age, diagnosed with HCD, participated in a 12- week, prospective, open-label trial with reboxetine (4-8 mg/d). They were examined for changes in: ADHD symptoms, as measured by the Conners Abbreviated (10-item) Teacher Rating Scale, aggression, as measured by the Yudofsky Overt Aggression Scale (OAS), impulsivity, as measured by the Plutchik impulsivity scale (IS), anxiety, as measured by the Revised Children's Manifest Anxiety Scale (RCMAS), and depressive mood, as measured by the Hamilton Rating Scale for Depression (HAM-D). RESULTS: There was a significant symptomatic improvement for HCD symptoms and associated symptoms. CONCLUSION: Our findings suggest that reboxetine may be effective in the treatment of HCD and associated symptoms.     

Effects of methylphenidate on adolescents with aggressive conduct disorder and ADDH: a preliminary report

The effect of methylphenidate on aggression in adolescents diagnosed with both aggressive conduct disorder and attention deficit disorder with hyperactivity was assessed in nine male adolescents. After three open trials, a placebo controlled double-blind design was used. During methylphenidate treatment of the six double-blind subjects, there was a significant reduction of aggressivity (p's less than 0.05), as measured by the Adolescent Antisocial Behavior Checklist. Conners Teacher Rating Scale Hyperactivity and Aggression scores were in the predicted directions, but the differences were not statistically significant.     

Citalopram treatment for impulsive aggression in children and adolescents: an open pilot study

OBJECTIVE: To assess the short-term effect and safety of citalopram in the reduction of impulsive aggression in children and adolescents. METHOD: Twelve subjects, aged 7 to 15 years, were attending a psychiatric outpatient clinic and had a profile of impulsive aggression. Subjects were treated in an open trial with citalopram for 6 weeks after a 1-week washout period. Dosage was regulated individually over a period of 4 weeks. The starting dose was 10 mg/day followed by 10 mg increments on a weekly basis. The maximum dose was not to exceed 40 mg/day. Outcome measures included the Modified Overt Aggression Scale (MOAS), the Child Behavioral Checklist (CBCL), and the Clinical Global Impressions (CGI). RESULTS: Eleven subjects completed the study Citalopram produced clinically and statistically significant reductions on target symptoms of impulsive aggression, independent of other behavioral problems, as measured by the MOAS, the CBCL, and the CGI at doses ranging from 20 to 40 mg/day (mean = 27 mg). No major adverse reactions were associated with citalopram use. CONCLUSION: Citalopram appears to be effective and well tolerated in this sample of children and adolescents with impulsive aggression.     

Development and validation of the outburst monitoring scale for children and adolescents

OBJECTIVE: The aim of this study was to develop a parent-completed questionnaire measure of specific types of aggressive behaviors in children and adolescents. METHOD: Two studies tested the psychometrics of the Outburst Monitoring Scale (OMS), a questionnaire measure of verbal, property, self, and physical aggression, based in part on the categories of the Overt Aggression Scale. In Study 1, parents of 23 adolescents with a history of aggressive-disruptive behavior and 30 control adolescents completed the OMS and other measures of aggressive-disruptive behavior. In Study 2, parents of 9 adolescents with a history of aggressive-disruptive behavior completed the OMS and other measures of aggressive-disruptive behavior during open-label treatment with methylphenidate and quetiapine. RESULTS: Results from both studies demonstrated adequate internal consistency of OMS subscale and total scores. OMS scores correlated significantly with measures of conduct disorder and oppositional defiant disorder and differentiated between control and aggressive sub-samples. Changes in OMS scores during treatment correlated with changes in other measures of aggressive and disruptive behavior. CONCLUSION: The OMS demonstrated good internal consistency, strong correlations with other measures of aggressive/disruptive behavior, good differential validity, and sensitivity to change during a medication trial. The OMS offers a quick, valid, questionnaire-based alternative for measuring frequencies of specific aggressive behaviors in clinical and research settings.     

A pilot controlled trial of topiramate for mania in children and adolescents with bipolar disorder

OBJECTIVE: To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type I. METHOD: This double-blind, placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy. Efficacy end points included the Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale for Children, Children's Depression Rating Scale, Children's Global Assessment Scale, and Clinical Global Impressions-Improvement. RESULTS: Fifty-six children and adolescents (6-17 years) with a diagnosis of bipolar disorder type I received topiramate (n=29, 52%) or placebo (n=27, 48%). The only statistically significant differences in efficacy measures between treatment groups were the difference between slopes of the linear mean profiles of the YMRS (p=.003) using a post hoc repeated measures regression and the change in Brief Psychiatric Rating Scale for Children at day 28 (-14.9 versus-5.9, p=.048) using observed data. Adverse events with topiramate included decreased appetite, nausea, diarrhea, and paresthesia. CONCLUSIONS: Topiramate was well tolerated; however, the results are inconclusive because of premature termination resulting in a limited sample size. Adequately powered controlled trials are necessary to determine whether topiramate has efficacy in reducing symptoms of acute mania in children and adolescents.     

A pilot study of quetiapine treatment of aggression due to traumatic brain injury

In a 6-week open-label, flexible dose pilot study of quetiapine for treatment of aggression secondary to traumatic brain injury (TBI), seven subjects who were at least 3-months post-injury were enrolled. The Overt Aggression Scale - Modified (OAS-M) and Clinical Global Impression (CGI) were primary outcome measures. Administration of quetiapine at doses of 25 to 300 mg daily was efficacious and well-tolerated in reducing irritability and aggression resulting from TBI, with an associated improvement in cognitive functioning.     

Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder.

OBJECTIVE: The study compared the safety and efficacy of sertraline, a selective serotonin reuptake inhibitor, and placebo in the treatment of generalized anxiety disorder in children and adolescents. METHOD: The study subjects were 22 children and adolescents age 5-17 years who met the DSM-IV criteria for generalized anxiety disorder according to the Anxiety Disorders Interview Schedule for Children-Revised and who had a Hamilton Anxiety Rating Scale score > or = 16. The patients underwent a 2-3-week prestudy evaluation period, followed by a 9-week double-blind treatment phase in which they were randomly assigned in blocks of four to receive either sertraline or pill placebo. The maximum dose of sertraline was 50 mg/day. Primary outcome measures were the Hamilton anxiety scale and the Clinical Global Impression scale. RESULTS: The Hamilton anxiety scale total score, psychic factor, and somatic factor and the Clinical Global Impression severity and improvement scales showed significant differences with treatment in favor of sertraline over placebo beginning at week 4. Self-report measures reflected these results at the end of treatment. CONCLUSIONS: The results of this double-blind, placebo-controlled trial suggest that sertraline at the daily dose of 50 mg is safe and efficacious for the treatment of generalized anxiety disorder in children and adolescents.     

An open-label study of lamotrigine adjunct or monotherapy for the treatment of adolescents with bipolar depression

OBJECTIVE: The treatment of pediatric bipolar depression has not been well studied. The authors wished to prospectively study the efficacy of lamotrigine as adjunctive or monotherapy in adolescents with bipolar disorder who were experiencing a depressive episode. METHOD: This was an 8-week open-label trial of lamotrigine with 20 adolescents ages 12-17 years (mean age 15.8; 7 boys, 13 girls) with diagnoses of bipolar disorder I, II, or not otherwise specified, who were experiencing a depressive episode. Lamotrigine was begun at 12.5 to 25 mg/day. Primary response criteria was a 1 or a 2 on the Clinical Global Impression-Improvement at week 8. A secondary criterion was at least a 50% decrease in Children's Depression Rating Scale-Revised scores. RESULTS: Nineteen subjects completed the trial. The mean final dose was 131.6 mg/day. Seven subjects were taking other psychotropic medications. Sixteen subjects (84%) responded by primary criteria, and 12 (63%) responded to our secondary criteria. Eleven subjects (58%) were considered in remission at week 8. Young Mania Rating Scale and Overt Aggression Scale-Modified scores also decreased significantly during the trial. There was no significant weight change, rash, or other adverse effects during the trial. CONCLUSIONS: Adolescents with bipolar depression appeared to respond to lamotrigine treatment, whether as adjunctive therapy or monotherapy, with decreases in depression, mania, and aggression. Larger, placebo-controlled studies of lamotrigine are needed in this population.     

Fluoxetine versus placebo in preventing relapse of major depression in children and adolescents

OBJECTIVE: The authors compared fluoxetine and placebo in continuation treatment to prevent relapse of major depressive disorder in children and adolescents. METHOD: After a detailed evaluation, children and adolescents 7-18 years of age with major depressive disorder were treated openly with fluoxetine. Those who had an adequate response after 12 weeks, as indicated by a Clinical Global Impression improvement score of 1 or 2 and a decrease of at least 50% in Children's Depression Rating Scale-Revised score, were randomly assigned to receive fluoxetine or placebo for an additional 6 months. The primary outcome measures were relapse and time to relapse. Relapse was defined as either a score of 40 or higher on the Children's Depression Rating Scale with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. Additional analyses were conducted with relapse defined only as a score of 40 or higher on the Children's Depression Rating Scale. RESULTS: Of 168 participants enrolled in acute fluoxetine treatment, 102 were randomly assigned to continuation treatment with fluoxetine (N=50) or placebo (N=52). Of these, 21 participants (42.0%) in the fluoxetine group relapsed, compared with 36 (69.2%) in the placebo group, a significant difference. Similarly, under the stricter definition of relapse, fewer participants in the fluoxetine group relapsed (N=11; 22.0%) than in the placebo group (N=25; 48.1%). Time to relapse was significantly shorter in the placebo group. CONCLUSIONS: Continuation treatment with fluoxetine was superior to placebo in preventing relapse and in increasing time to relapse in children and adolescents with major depression.     

Characterizing Aggressive and Noncompliant Behaviors in a Children’s Psychiatric Inpatient Setting

This study was conducted to evaluate aggression and noncompliance among child psychiatric inpatients in relation to demographic, clinical, and hospitalization characteristics, including the use of restraints and seclusion. Eighty six children (10.8±2.4 years old, 67% male) consecutively admitted to an inpatient psychiatric unit were rated weekly using the Modified Overt Aggression Scale (MOAS) and the Disruptive Behavior Rating Scale (DBRS) between November 1, 2002 and June 30, 2003. Moderate to high correlations were observed between the four types of aggression (verbal, and physical against self, others, or objects) and noncompliant behavior. In hierarchical regression analyses, only mental retardation emerged as a significant predictor of aggression and noncompliance. Aggression and noncompliance were associated with different characteristics of inpatient treatment. Aggressive behavior was significantly associated with the use of restraints and seclusion, and noncompliant behavior with length of hospitalization and number of psychiatric medications at time of discharge. Modifying milieu interventions for youths with mental retardation, and adapting behavioral interventions empirically proven to target noncompliance may be effective loci for reducing aggression in child psychiatric inpatient units.     

Comparison of the suicidal behavior of adolescent inpatients with borderline personality disorder and major depression

The objective of the study was to examine the hypothesis that some forms of suicidal behavior among adolescents are related to helplessness and depression, whereas others are related to anger and impulsivity. Sixty-five adolescents were studied. Thirty-three had borderline personality disorder (BPD), of whom 17 had made a recent suicide attempt. Thirty-two had major depressive disorder (MDD), of whom 16 had made a recent suicide attempt. Assessments were made with the Child Suicide Potential Scale, the Beck Depression Inventory, the Beck Hopelessness Scale, the Multidimensional Anger Inventory, the Overt Aggression Scale, the Impulsiveness-Control Scale, and the Suicide Intent Scale. Adolescents with BPD had more anger, aggression, and impulsiveness than those with MDD, but similar levels of depression and hopelessness. Suicidal versus nonsuicidal adolescents were more depressed, hopeless, and aggressive, but not more angry or impulsive. There were no significant differences in impulsiveness for the MDD suicidal group versus the MDD nonsuicidal group, but the suicidal BPD adolescents were significantly more impulsive than the nonsuicidal BPD adolescents. In the subjects with BPD, impulsiveness and aggression correlated significantly and positively with suicidal behavior. In the subjects with MDD, no such correlations were seen. In both diagnostic groups, depression and hopelessness correlated positively and significantly with suicidal behavior. Anger did not correlate with suicidal behavior in either of the groups. The suicidal subjects with MDD had significantly higher suicidal intent scores than the suicidal adolescents with BPD. We conclude that the nature of suicidal behavior in adolescents with BPD differs from that seen in MDD with respect to the role of anger and aggression.     

A preliminary double-blind, placebo-controlled trial of divalproex sodium in borderline personality disorder

BACKGROUND: Borderline personality disorder is characterized by affective instability, impulsivity, and aggression and is associated with considerable morbidity and mortality. Since anticonvulsant agents may be helpful in such symptomatology, we compared divalproex sodium with placebo in patients with borderline personality disorder. METHOD: A 10-week, parallel, double-blind design was conducted. Sixteen outpatients meeting Structured Clinical Interview for DSM-IV Axis II Personality Disorders criteria for borderline personality disorder were randomly assigned to receive placebo (N = 4) or divalproex sodium (N = 12). Change was assessed in global symptom severity (Clinical Global Impressions-Improvement Scale [CGI-I]) and functioning (Global Assessment Scale [GAS]) as well as in specific core symptoms (depression, aggression, irritability, and suicidality). RESULTS: There was significant improvement from baseline in both global measures (CGI-I and GAS) following divalproex sodium treatment. A high dropout rate precluded finding significant differences between the treatment groups in the intent-to-treat analyses, although all results were in the predicted direction. CONCLUSION: Treatment with divalproex sodium may be more effective than placebo for global symptomatology, level of functioning, aggression, and depression. Controlled trials with larger sample sizes are warranted to confirm these preliminary results.     

Citalopram,a selective serotonin reuptake inhibitor,in the treatment of aggression in schizophrenia

The aim of this double-blind cross-over study was to investigate whether treatment with the selective serotonin reuptake inhibitor, citalopram reduces aggressiveness in chronically violent schizophrenic inpatients. Initially 19 patients were enrolled into this double-blind cross-over study in which the patients were treated for 24 weeks with placebo and 24 weeks with citalopram (20–60 mg/day) as a supplement to their previous neuroleptic medication. Fourteen patients completed the entire study, but sufficient data on 15 patients could be used in the end–point analysis of efficacy. Psychiatric assessments (Brief Psychiatric Rating Scale, Clinical Global Impression Scale for Severity of Illness, Social Dysfunction and Aggression Scale and the Global Aggression Scale) and side effects (UKU Side Effect Scale) were recorded at baseline and 4 times during both periods. Aggressive incidents (Staff Observation Aggression Scale) were recorded throughout the study. During citalopram treatment, the frequency of aggressive incidents was significantly lower and the mental state did not deteriorate. Patients either experienced no side effects or else side effects were equally mild during both periods.     

Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial

BackgroundA case series suggested efficacy for lithium to treat agitation in dementia, but no placebo-controlled trials have been conducted.ObjectivesTo evaluate low-dose lithium treatment of agitation in Alzheimer's disease (AD).MethodIn a four-site trial, patients with AD and agitation/aggression score ≥4 on the Neuropsychiatric Inventory (NPI) were randomized, double-blind, to lithium carbonate 150–600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response (30% reduction in NPI score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved). Safety profile of lithium was assessed.ResultsFifty-eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium was not significantly superior to placebo for agitation/aggression. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ²=1.26, p = 0.26). Moderate or marked improvement (CGI) was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher's exact test p <0.001). In exploratory analyses, improvement on lithium was greater than placebo on NPI delusions and irritability/lability (p's<0.05). Lithium showed greater reduction than placebo in patients with high Young Mania Rating Scale scores (β=5.06; 95%CI,1.18 to 8.94, p = 0.01). Oral dose and serum levels demonstrated similar associations with efficacy outcomes. Lithium did not differ significantly from placebo on safety outcomes.ConclusionsLow-dose lithium was not efficacious in treating agitation but was associated with global clinical improvement and excellent safety. A larger trial may be warranted of likely lithium-responsive behavioral symptoms that overlap with mania.