A randomized controlled pilot trial of vilazodone for adult separation anxiety disorder.

BACKGROUND: Separation anxiety disorder was recently recognized by fifth edition of the Diagnostic and Statistical Manual of Mental Disorders as a diagnosis in adults, but no publications to date have characterized a sample of patients seeking treatment for adult separation anxiety disorder (ASAD) or assessed treatment efficacy. We hypothesized that vilazodone, a selective serotonin reuptake inhibitor (SSRI) and serotonin 1a (5HT1a ) receptor partial agonist, would have efficacy in ASAD, because SSRIs have appeared efficacious in children with mixed diagnoses including separation anxiety disorder and in animal models of separation anxiety. METHODS: In this pilot study, 24 adults (ages 18-60) with a principal diagnosis of ASAD were randomized to 12 weeks of double-blind treatment with vilazodone (n = 13) or placebo (n = 11). Outcome was assessed by an independent evaluator and self-ratings, and analyzed with mixed effect models. RESULTS: This sample was predominantly female (67%), with comorbid psychiatric disorders (58%), and adult onset of separation anxiety disorder (62%). Response rates at week 12 did not differ significantly between groups. Across all time points, the vilazodone group evidenced greater improvement on the Structured Clinical Interview for Separation Anxiety Symptoms (P = .026) and the Quality of Life Enjoyment and Satisfaction Questionnaire (P = .011), and trends toward greater improvement on the Adult Separation Anxiety Questionnaire (P = .054) and the Clinical Global Impression-Change Scale (P = .086), all with large between-group effect sizes. CONCLUSIONS: Findings demonstrate feasibility of a clinical trial in ASAD, and they suggest that vilazodone may have efficacy in the treatment of ASAD and warrants further study.

Dogs with separation-related problems show a "less pessimistic" cognitive bias during treatment with fluoxetine (Reconcile™) and a behaviour modification plan.

BACKGROUND: Canine separation-related problems (SRP) (also described as "separation anxiety" or "separation distress") are among the most common behavioural complaints of dog owners. Treatment with psychoactive medication in parallel with a behaviour modification plan is well documented in the literature, but it is unknown if this is associated with an improvement in underlying affective state (emotion and mood) or simply an inhibition of the behaviour. Cognitive judgement bias tasks have been proposed as a method for assessing underlying affective state and so we used this approach to identify if any change in clinical signs during treatment was associated with a consistent change in cognitive bias (affective state). Five dogs showing signs of SRP (vocalising - e.g. barking, howling-, destruction of property, and toileting - urination or defecation- when alone) were treated with fluoxetine chewable tablets (Reconcile™) and set on a standard behaviour modification plan for two months. Questionnaires and interviews of the owners were used to monitor the clinical progress of the dogs. Subjects were also evaluated using a spatial cognitive bias test to infer changes in underlying affect prior to, and during, treatment. Concurrently, seven other dogs without signs of SRP were tested in the same way to act as controls. Furthermore, possible correlations between cognitive bias and clinical measures were also assessed for dogs with SRP. RESULTS: Prior to treatment, the dogs with SRP responded to ambiguous positions in the cognitive bias test negatively (i.e. with slower running speeds) compared to control dogs (p < 0.05). On weeks 2 and 6 of treatment, SRP dogs displayed similar responses in the cognitive bias test to control dogs, consistent with the possible normalization of affect during treatment, with this effect more pronounced at week 6 (p > 0.05). Questionnaire based clinical measures were significantly correlated among themselves and with performance in the cognitive bias test. CONCLUSION: These results demonstrate for the first time that the clinical treatment of a negative affective state and associated behaviours in a non-human species can produce a shift in cognitive bias. These findings demonstrate how the outcome of an intervention on a clinical problem can be evaluated to determine not only that the subject's behaviour has improved, but also its psychological state (welfare).

Auraptene exerts protective effects on maternal separation stress-induced changes in behavior, hippocampus, heart and serum of mice.

Early life stress is associated with various complications. Auraptene has significant antioxidant and anti-inflammatory effects. This study aimed to assess the probable underlying mechanisms that mediate changes in the behavior, hippocampus, heart and serum in the mouse model of maternal separation (MS) stress. We evaluated the possible protective effects of auraptene in these changes focusing on inflammatory response and oxidative state. Mice were treated with auraptene (5, 10, and 50 mg/kg). In addition, anxiety-like behaviors were evaluated using behavioral tests; including open field test (OFT) and elevated plus maze (EPM). Hippocampus and heart samples were assessed histopathologically. Levels of malondialdehyde (MDA) and antioxidant capacity, as well as nitrite levels, were measured in serum, heart, and hippocampal tissues. Moreover, gene expression of inflammatory markers (Il-1ß and Tlr-4) was evaluated in the heart and hippocampus. Results showed that auraptene reversed the negative effects of MS on behavior (increased time spent in central zone of the OFT and time and entries to the open arms of the EPM). Auraptene mitigated adverse effects of MS on the hippocampus (increased diameter and decreased percentage of dark neurons in the CA3 area). Accordingly, auraptene decreased MDA and nitrite levels and increased the antioxidant capacity in serum, and hippocampal samples. However, we observed different effects for different doses of auraptene in the heart samples. We concluded that MS is associated with anxiety-like behavior and cellular/molecular modifications in the heart, hippocampus and serum. We found that auraptene exerted protective effects against these negative effects of MS in mouse.

Efficacy of dog-appeasing pheromone (DAP) for ameliorating separation-related behavioral signs in hospitalized dogs.

Dogs hospitalized in veterinary clinics are likely to show signs of separation-induced anxiety from hospitalization. The study assessed the effect of dog-appeasing pheromone (DAP) on 10 typical separation-related behavioral signs in hospitalized dogs. A DAP treated group (n = 24) was compared with a placebo control group (n = 19). There was overall amelioration of the signs without 'vigilance' and 'anorexia' in the DAP-treated dogs; marked decreases were noted in elimination (P = 0.038), excessive licking (P = 0.005), and pacing (P = 0.017). The results suggest that the use of DAP could decrease separation-induced anxiety, distress, and fear in inpatients, and possibly facilitate recovery in hospitalized dogs.

AMBMP activates WNT pathway and alleviates stress-induced behaviors in maternal separation and chronic stress models.

Depressive disorders are both prevalent and debilitating, and a proportion of patients have treatment resistance to classic antidepressants. Recent evidence has implicated the intracellular WNT signaling pathway as having a key role in the pathogenesis of major depressive disorder. In the present study, we investigated the role of ß-catenin and transcription factor-4 (TCF4) in the depression-like and anxiety-like behaviors exhibited by mice exposed to maternal separation, or chronic mild stress. Both rodent models of childhood and adulthood stress showed depression and anxiety-like behaviors. During the last three weeks of medication, we applied AMBMP (2-Amino-4-[3,4- (methylenedioxy)benzylamino]-6-(3-methoxyphenyl)pyrimidine) to the maternal separation and chronic stress model for the first time. The drug alleviated the depression-like index in saccharin preference test (SPT) and forced swim test (FST), and anxiety-like index in open field test (OFT) and elevated-plus maze (EPM), and reversed the disruption of ß-catenin and TCF4 in stressed mice by upregulating the WNT pathway specifically. Therefore, the WNT pathway may be involved in the mediation of patient recovery and could be a target for novel antidepressants.

Pancreatitis associated with clomipramine administration in a dog.

A three-year-old, male, entire, Yorkshire terrier was presented with peracute onset of abdominal pain and vomitus. Clinicopathological abnormalities included severely increased serum lipase activity, immeasurably high serum trypsin-like immunoreactivity and mild hypocalcaemia. Canine pancreatic lipase immunoreactivity (cPLI) was intended to be measured, however, the sample got lost. Ultrasonography revealed a hypoechoic pancreas with small amounts of peripancreatic fluid and hyperechogenic mesentery. Acute pancreatitis (AP) was diagnosed and the dog recovered with appropriate therapy within 48 hours. Clomipramine, a selective serotonin reuptake inhibitor (SSRI) for alleviating signs of separation anxiety had been given for seven weeks. Two similar, albeit less severe, episodes associated with previous courses of clomipramine had occurred eight months earlier that responded to discontinuing clomipramine and supportive care. As SSRIs are associated with AP in human beings and no other trigger could be identified, we conclude that clomipramine should be considered as a potential cause when investigating causes for AP in susceptible breeds or other dogs presenting with compatible clinical signs.

[Psychodynamic psychopharmacology in clinical practice--interpretations of adverse events of pharmacotherapy. Case report]. / Psychodynamiczna psychofarmakologia w praktyce--mozliwosci interpretacji dzialan niepozadanych farmakoterapii. Opis przypadku.

INTRODUCTION: Psychodynamic psychopharmacology offers possibility of implementation of psychodynamic thinking and interpretations in the process of pharmacotherapy of mental disorders. It can be helpful in improving results of treatment and solving difficulties in it's course. METHOD: The case report of a female patient after psychotic episode is presented. During the treatment with quetiapine the patient presented complains about adverse effects like weight gain and somnolence. These symptoms (at least partially) resulted from her emotional problems and changed after psychodynamic interpretation. After stopping the medication the patient's reactions to stress and process of separation from her mother changed dramatically. It was probably due to the discontinuation of medication. RESULTS: In some cases adverse events of medication have not only biological but also emotional roots. If properly recognized they can be interpreted and changed by psychological tools. CONCLUSIONS: Psychodynamic psychopharmacology can be useful in deeper understanding and solving problems in the process of pharmacotherapy of mental disorders.

[Pharmacotherapy for social phobia, generalised anxiety disorder and separation anxiety disorder in children and adolescents: an overview]. / Farmacotherapie bij sociale fobie, gegeneraliseerde angststoornis en separatieangststoornis bij kinderen en adolescenten: Een literatuuroverzicht.

BACKGROUND: Anxiety disorders are among the most prevalent psychiatric disorders during childhood. They are often persistent and are associated with a number of negative outcomes. Therefore, effective treatment is required. AIM: To present an overview of placebo-controlled studies of pharmacotherapy for social phobia, generalised anxiety disorder and separation anxiety disorder in children an adolescents and to determine which medication is the most effective. METHOD: The literature was reviewed using Pubmed. RESULTS: Nine randomised double-blind studies on the efficacy of pharmacotherapy for generalised anxiety disorder, separation anxiety disorder and social phobia were found. Tricyclic antidepressants were not more effective than placebo. Studies on benzodiazepines showed that the effect of these drugs was not superior to that of placebo either. Studies of the efficacy of ssris, however, proved that they were superior to placebo. CONCLUSION: SSRIS are the drugs of first choice for the treatment of social phobias, separation anxiety disorder and generalised anxiety disorder in children and adolescents. There is strong evidence that ssris are effective for the treatment of these anxiety disorders; the standardised effect size varies between medium and large.

affron®, a standardised extract from saffron (Crocus sativus L.) for the treatment of youth anxiety and depressive symptoms: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Saffron has antidepressant and anxiolytic effects in adults with mild-to-moderate depression. However, this is the first study examining its mood-related effects in teenagers. METHODS: In this 8-week, randomised, double-blind, placebo-controlled study, youth aged 12-16 years, with mild-to-moderate anxiety or depressive symptoms were given tablets containing placebo or a saffron extract (affron®, 14 mg b.i.d). The youth and parent versions of the Revised Child Anxiety and Depression Scale (RCADS) were used as outcome measures. RESULTS: 80 participants were enrolled and 68 completed the study. Based on youth self-reports, affron® was associated with greater improvements in overall internalising symptoms (p = 0.049), separation anxiety (p = 0.003), social phobia (p = 0.023), and depression (p = 0.016). Total internalising scores decreased by an average of 33% compared to 17% in the placebo group (p = 0.029). However, parental reports of improvements were inconsistent as mean improvements in RCADS scores were greater in the saffron group (40% vs 26%) (p = 0.026), although no other significant differences were identified. affron® was well-tolerated and there was a trend of reduced headaches in participants on the active treatment. LIMITATIONS: The use of a self-report instrument, limited study duration, single treatment dose, and non-clinical sample used in this study limit the generalisability of study findings. CONCLUSION: The administration of a standardised saffron extract (affron®) for 8 weeks improved anxiety and depressive symptoms in youth with mild-to-moderate symptoms, at least from the perspective of the adolescent. However, these beneficial effects were inconsistently corroborated by parents.

Effects of different doses of intranasal dexmedetomidine on preoperative sedation and postoperative agitation in pediatric with total intravenous anesthesia undergoing adenoidectomy with or without tonsillectomy.

Dexmedetomidine is a highly selective α2 receptor agonist, this study aimed to investigate the effects of different doses of intranasal dexmedetomidine on the preoperative sedation and postoperative agitation in pediatric with total intravenous anesthesia (TIVA) for adenoidectomy with or without tonsillectomy.This is a double-blind placebo-controlled randomized trial. Pediatric were randomly divided into the D1, D2, and S groups, each group contained 30 patients. Twenty-five to 40 minutes before surgery, the D1 and D2 groups received intranasally dexmedetomidine 1 µg kg or 2 µg kg, respectively, while the S group received saline of the same volume. A unified protocol of TIVA induction and maintenance was used for the three groups. The preoperative sedation, behavior of separation from parents, postoperative agitation, and postoperative pain of the children were evaluated.The proportions of satisfactory sedation in the D1, D2, and S groups were 63.3%, 76.7%, and 0%, respectively. There was a statistically significant difference between D1 and S groups (P = .000) and D2 versus S groups (P = .000), while there was no statistically significant difference between D1 and D2 groups (P = .399). As for scale on the behavior of separation from parents, there was a statistically significant difference between D1 and S groups (P = .009) and D2 versus S groups (P = .009), whereas there was no significant difference between D1 and D2 groups (P = 1). The incidence of postoperative agitation in the D1, D2, and S groups was 43.3%, 30.0%, and 63.3%, respectively, and there was a statistical difference between D2 and S groups (P = .010). There was a significant difference in the Pediatric Anesthesia Emergence Delirium (PAED) scale between D2 and S groups (P = .029). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) in the D2 group was significantly lower than the S group (P = .013).The intranasal dexmedetomidine of 1 or 2 µg kg 25 to 40 minute before induction of anesthesia both could deliver effective preoperative sedation, reducing the children's distress of separation from parents. Moreover, intranasal dexmedetomidine of 2 µg kg could deliver more effective postoperative analgesia and reduce postoperative agitation, without prolonging postoperative recovery or causing severe adverse events.

Sleep-related problems among children and adolescents with anxiety disorders.

OBJECTIVE: The present study examined sleep-related problems (SRPs) among a large sample (n = 128) of youth with anxiety disorders (i.e., generalized, separation, and social). The frequency of eight specific SRPs was examined in relation to age, gender, type of anxiety disorder, anxiety severity, and functional impairment. The impact of pharmacological treatment (fluvoxamine versus pill placebo) in reducing SRPs also was examined. METHOD: As part of a large, double-blind, randomized, controlled trial (Research Units on Pediatric Psychopharmacology Anxiety Study Group), clinician and parent reports of SRPs were examined among children and adolescents, ages 6 to 17 years, before and after treatment. RESULTS: Eighty-eight percent of youth experienced at least one SRP, and a majority (55%) experienced three or more. Total SRPs were positively associated with anxiety severity and interference in family functioning. Significantly greater reductions in SRPs were found among children treated with fluvoxamine compared with placebo. CONCLUSIONS: These findings indicate that SRPs are commonly associated with childhood anxiety disorders and suggest a need for the assessment of and attention to these problems in research and clinical settings.

Effects of reconcile (fluoxetine) chewable tablets plus behavior management for canine separation anxiety.

Canine separation anxiety is a common behavioral problem presented to veterinarians. Associated behaviors are distressing to both dog and owner, have the potential to disrupt the human-companion animal bond, and may lead to euthanasia. The results of this study demonstrate the clinical efficacy and safety of Reconcile (fluoxetine, 1 to 2 mg/kg/day [0.45 to 0.91 mg/lb/day]), in conjunction with behavior management, for the treatment of canine separation anxiety. The beef flavored chewable formulation was palatable to treated dogs and easy to administer. This study provides to veterinarians and owners valuable information about an effective separation anxiety treatment plan that combines use of Reconcile with behavior modification.

Penile self-mutilation as an unusual sign of a separation-related problem in a crossbreed dog.

A two-year-old, male, crossbreed dog was presented for evaluation of licking, biting and severe self-mutilation of its penis, which resulted in ulcers and haemorrhagic preputial discharge. History revealed signs of separation anxiety such as active greeting behaviour, excessive vocalisation and intermittent episodes of licking of the penis when the dog was left alone. The owner reported that he had been hospitalised after a car accident, and he had no chance of seeing the dog. During that time, the behaviour progressed to frequent episodes of licking and biting of the penis. Three weeks of treatment with clomipramine in addition to the presence of the dog's brother, who was brought into the dog's living environment, appeared to produce a considerable degree of improvement. The purpose of this report is to contribute to an increased awareness within veterinary practice of unusual signs of separation anxiety such as penile self-mutilation.

Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial.

OBJECTIVE: This is a feasibility study evaluating the safety, tolerability, and potential anxiolytic efficacy of the α2 agonist guanfacine extended-release (GXR) in children and adolescents with generalized anxiety disorder (GAD), separation anxiety disorder (SAD), or social phobia/social anxiety disorder. METHODS: Youth aged 6-17 years with a primary diagnosis of GAD, SAD, and/or social anxiety disorder were treated with flexibly dosed GXR (1-6 mg daily, n = 62) or placebo (n = 21) for 12 weeks. The primary aim of this study was to determine the safety and tolerability of GXR in youth with anxiety disorders, which involved the analysis of treatment-emergent adverse events (TEAEs), the emergence of suicidal ideation and behaviors, vital signs, and electrocardiographic/laboratory parameters. Exploratory efficacy measures included dimensional anxiety scales (Pediatric Anxiety Rating Scale [PARS] and Screen for Child Anxiety Related Emotional Disorders [SCARED]), as well as the Clinical Global Impression-Improvement (CGI-I) scale. As this was an exploratory study, no inferential statistical analyses were performed. RESULTS: GXR was safe and well tolerated. Treatment-related mean ± standard deviation changes in heart rate (GXR: 1.8 ± 12 beats per minute [bpm] decrease; placebo: 0.5 ± 11 bpm decrease), systolic blood pressure (GXR: 2.3 ± 11 mm Hg decrease; placebo: 1.7 ± 11 mm Hg decrease), or diastolic blood pressure (GXR: 1.3 ± 9 mm Hg decrease; placebo: 0.9 ± 7 mm Hg increase) were similar between treatment groups. TEAEs, including headache, somnolence/fatigue, abdominal pain, and dizziness, were consistent with the known safety profile of GXR. No differences were observed between treatment groups for PARS and SCARED scores, although at endpoint, a higher proportion of subjects receiving GXR versus placebo demonstrated CGI-I scores ≤2 (54.2% vs. 31.6%), as rated by the clinician investigator. CONCLUSIONS: GXR was well tolerated in pediatric subjects with GAD, SAD, and/or social anxiety disorder. ClinicalTrials.gov Identifier: NCT01470469.

Anxiolytic-like properties of the anandamide transport inhibitor AM404.

The endocannabinoids anandamide and 2-arachidonoyglycerol (2-AG) may contribute to the regulation of mood and emotion. In this study, we investigated the impact of the endocannabinoid transport inhibitor AM404 on three rat models of anxiety: elevated plus maze, defensive withdrawal and separation-induced ultrasonic vocalizations. AM404 (1-5 mg kg(-1), intraperitoneal (i.p.)) exerted dose-dependent anxiolytic-like effects in the three models. These behavioral effects were associated with increased levels of anandamide, but not 2-AG, in the prefrontal cortex and were prevented by the CB(1) cannabinoid antagonist rimonabant (SR141716A), suggesting that they were dependent on anandamide-mediated activation of CB(1) cannabinoid receptors. We also evaluated whether AM404 might influence motivation (in the conditioned place preference (CPP) test), sensory reactivity (acoustic startle reflex) and sensorimotor gating (prepulse inhibition (PPI) of the startle reflex). In the CPP test, AM404 (1.25-10 mg kg(-1), i.p.) elicited rewarding effects in rats housed under enriched conditions, but not in rats kept in standard cages. Moreover, AM404 did not alter reactivity to sensory stimuli or cause overt perceptual distortion, as suggested by its lack of effect on startle or PPI of startle. These results support a role of anandamide in the regulation of emotion and point to the anandamide transport system as a potential target for anxiolytic drugs.

Bipolar disorder and comorbid anxiety disorders in children and adolescents.

Recent attention has focused on the association between bipolar disorder and comorbid anxiety disorders in children and adolescents. There is a high rate of comorbidity between bipolar disorder and anxiety disorders in children and youths. Often, a child or adolescent with bipolar disorder has multiple comorbid anxiety disorders. In general, anxiety disorders precede the development of bipolar disorder in children. Comorbid disorders may worsen the course of each individual disorder. Pharmacologic management of the comorbid anxiety disorder is complicated by potential mood destabilization in a child or adolescent with bipolar disorder.

Evaluation of antioxidant effect of Nerium indicum in anxious rats.

AIM: The aim of this study was to analyze the ethyl acetate extract of Nerium indicum (NIE) flower for its antioxidant effect in anxious Sprague-Dawley rats. MATERIALS AND METHODS: Animals were divided into six groups (n = 6) and treated with 200 mg/kg and 400 mg/kg p.o. of NIE for 21 days to assess its preventive and curative effects. Anxiety was induced by isolating animals socially for 21 days. Elevated plus maze (EPM) and light and dark model were used for measuring anxiety in animals. Oxidative stress parameters such as lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) in blood and brain tissue homogenate were monitored after 21 days of social isolation in animals. RESULTS: Rats were treated with NIE 200 mg/kg and 400 mg/kg p.o. Both the treatments showed a significant (P < 0.001) increase in the number of open arm entries and time spent in open arm in EPM when compared with the negative control. Results also demonstrated that there was a significant (P < 0.001) increase in the number of lightbox entries and time spent in light box in light and dark model when compared with negative control. There was a significant (P < 0.001) improvement in endogenous anti-oxidants such as SOD, CAT, reduced GSH, and decreased levels of LPO in blood and brain tissue when compared with the negative control. CONCLUSION: The present study suggests the role of NIE in the treatment of anxiety, possibly by modulating the oxidative stress.

Screening antidepressants in the chick separation-stress paradigm.

RATIONALE: Clinical research has indicated that antidepressants are efficacious in the treatment of anxiety disorders, especially when repeatedly administered. However, few animal models of anxiety are sensitive to antidepressants, a finding that may be due to procedures limited to acute administrations. OBJECTIVES: The purpose of the present research was to further validate the chick separation-stress paradigm as an animal model of anxiety by examining its sensitivity to the monoamine oxidase inhibitor (MAOI) phenelzine (6.25, 12.5, 25.0 mg/kg), the tricyclic antidepressant (TCA) imipramine (5.0, 10.0, 20.0 mg/kg), the selective serotonin reuptake inhibitor (SSRI) citalopram (1.0, 2.5, 5.0 mg/kg), and the norepinephrine reuptake inhibitor (NRI) maprotiline (5.0, 10.0, 20.0 mg/kg) under acute (no pretreatment) or repeated (3 or 6 days pretreatment) administration procedures. METHODS: Following any pretreatment, 8-day-old chicks received their respective vehicle or drug probe injection 15 min before tests in either a "mirror" (low stress) or "no mirror" (high stress) condition for a 180-s isolation period. The dependent measures were distress vocalizations to index separation stress and sleep onset latency to index sedation. RESULTS: The model was sensitive to acutely administered phenelzine (MAOI), imipramine (TCA), and maprotiline (NRI), but not citalopram (SSRI) and retained its sensitivity to these drug probes across both repeated administration procedures. None of the drug probes possessed any sedative properties. CONCLUSIONS: These results help extend the validity and utility of the chick separation-stress paradigm as an animal model of anxiety by demonstrating its sensitivity to antidepressants under both acute and repeated administration procedures.

Fluoxetine for the treatment of childhood anxiety disorders: open-label, long-term extension to a controlled trial.

OBJECTIVE: To assess the efficacy of fluoxetine for the long-term treatment of children and adolescents with anxiety disorders, including generalized anxiety disorder, separation anxiety disorder, and/or social phobia. METHOD: Children and adolescents (7-17 years old) with anxiety disorders were studied in open treatment for 1 year after they completed a randomized, controlled trial (RCT) comparing fluoxetine and placebo. The follow-up phase assessments included clinician, parent, and child ratings with measures of global severity, global improvement, and anxiety symptoms. RESULTS: Subjects taking fluoxetine (n = 42) were compared with those taking no medication (n = 10) during follow-up on anxiety changes from the end of the RCT through the follow-up period. Statistical models included RCT assignment and follow-up psychological treatment. Excluded subjects took other medications (n = 4) or did not complete follow-up (n = 18). Compared with subjects taking no medication, subjects taking fluoxetine showed significantly superior follow-up outcomes on most measures, including clinician, parent, and child ratings. CONCLUSIONS: The results suggest that fluoxetine is clinically effective for the maintenance treatment of anxiety disorders in children and adolescents. A major limitation, however, was the lack of RCT methodology in the follow-up phase. RCTs are needed to determine the long-term risks and benefits of fluoxetine for this group.

Comparison of the efficacy of a synthetic dog-appeasing pheromone with clomipramine for the treatment of separation-related disorders in dogs.

Sixty-seven dogs that showed signs of distress when separated from their owners (destructiveness, excessive vocalisation and house soiling) and hyperattachment were used in a randomised, blind trial to assess the potential value of a dog-appeasing pheromone in reducing the unacceptable behaviours. For ethical reasons, there was no placebo group and the effects of the pheromone were compared with the effects of clomipramine which is regularly used to treat this type of problem. The undesirable behaviours decreased in both groups, but the overall assessment by the owners indicated that there was no significant difference between the two treatments, although there were fewer undesirable events in the dogs treated with the pheromone, and the administration of the pheromone appeared to be more convenient.