ABSTRACT
BACKGROUND: The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is a widely used semi structured clinician-rated interview to assess the presence and severity of obsessive-compulsive disorder (OCD). The scale is revised (Y-BOCS-II) to overcome several psychometric limitations, for example by extending the scoring for better discrimination within higher severity levels. AIM: To examine the responsiveness and other psychometric properties of the Y-BOCS-II in a Dutch clinical sample. METHOD: The Y-BOCS-II was translated into Dutch (Y-BOCS-II) and administered to 110 patients seeking therapy for OCD. This was done twice, before and after treatment. The original Y-BOCS was simultaneously rated. Self-report measures regarding depression, symptom severity and OCD symptoms were assessed. RESULTS: The Y-BOCS-II had a good internal consistency (Cronbach’s α = 0.84), test-retest (ICC = 0.81) and inter-rater reliability (ICC = 0.94). The construct validity proved to be modest to good. The responsiveness over time was in favour of the Y-BOCS-II, compared with the YBOCS-I, particularly in the severely affected OCD patients. CONCLUSION: The Y-BOCS-II severity scale is a reliable and valid instrument for accurately assessing the severity of OCD symptoms and for measuring treatment-induced change. This second version also has clinical and psychometric advantages over the YBOCS-I. When these findings are sufficiently replicated, use of the YBOCS-II as the new common standard seems recommendable.
Subject(s)
Obsessive-Compulsive Disorder , Humans , Psychometrics , Reproducibility of Results , Severity of Illness Index , Obsessive-Compulsive Disorder/diagnosis , Ethnicity , Psychiatric Status Rating ScalesABSTRACT
BACKGROUND: Preliminary studies have shown that the addition of the partial NMDA-agonist d-cycloserine (DCS) might be promising in enhancing the results of exposure therapy in obsessive-compulsive disorder (OCD). We examined the effect of DCS addition to exposure therapy in a somewhat larger sample of OCD patients with special attention to subgroups, because of the heterogeneity of OCD. METHODS: A randomized, double-blind, placebo controlled trial was conducted in 39 patients with OCD. Patients received 6 guided exposure sessions, once a week. One hour before each session 125mg DCS or placebo was administered. RESULTS: Scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) declined more in the DCS group than in the placebo group, but the difference did not reach statistical significance (P=0.076, partial η2=0.13). Response percentages also did not differ between the DCS and the placebo group (37% and 15% respectively). In the 'cleaning/contamination' subgroup a significant effect was found in favour of DCS (P=0.033, partial η2=0.297). CONCLUSIONS: The results of this study did not support the application of DCS to exposure therapy in OCD. Some specific aspects need further investigation: efficacy of DCS in a larger 'cleaning/contamination' (sub-)group, DCS addition only after successful sessions, interaction with antidepressants.
Subject(s)
Antidepressive Agents/administration & dosage , Cognitive Behavioral Therapy/methods , Cycloserine/administration & dosage , Obsessive-Compulsive Disorder/drug therapy , Adult , Combined Modality Therapy , Double-Blind Method , Female , Humans , Male , Middle Aged , Obsessive-Compulsive Disorder/therapy , Therapy, Computer-Assisted/methods , Treatment Outcome , Young AdultABSTRACT
Admissions for irreversible psychosurgical treatment of obsessive-compulsive disorder (OCD) by the Working Group for Indication Psychosurgery in the Netherlands were analyzed, and the postsurgical effects on symptom severity and quality of life were evaluated. The data were extracted from patient records in the period 2001-2008, and there was a postoperative assessment with a semistructured interview. Fourteen patients applied, having severe OCD with mostly one or more comorbid disorders. The mean Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score was 32 points. Four of seven patients in whom psychosurgery was deemed useful were operated on. The decrease of the Y-BOCS score from registration to after surgery was 9 points (range, 3-17 points). An improvement in social function was present in three of four patients. In conclusion, psychosurgery can be a valuable treatment option for patients with severe OCD in whom other treatments fail.
Subject(s)
Brain/surgery , Neural Pathways/surgery , Obsessive-Compulsive Disorder/surgery , Psychosurgery/methods , Adult , Caudate Nucleus/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Netherlands , Obsessive-Compulsive Disorder/physiopathology , Psychosurgery/adverse effects , Quality of Life , Severity of Illness Index , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Clinicians need to be well informed about staging and profiling so that they can divide patients with anxiety disorders into groups according to the phase and severity of their illness. The group to which the patient is assigned determines the types of treatment he or she receives. AIM: To investigate ways in which clinicians can be helped to apply staging and profiling procedures to patients with anxiety disorders. METHOD: We searched the literature for articles about the staging and profiling of anxiety disorders. RESULTS: There seems to be practically no literature relating to the staging and profiling of anxiety disorders. However, in daily practice clinicians do attempt to classify their patients and use forms of staging when deciding on special types of treatment for their patients and when assessing the length of treatment required. The revised Dutch guidelines on anxiety disorders include a generalised form of staging, called 'stepped care’. These revisions have been made on the basis of consensus decisions reached by the guideline committee. CONCLUSION: The revised guidelines on anxiety disorders assist clinicians with the application of staging in their daily practice. However, because of the lack of scientific data, our article closes with the presentation of a research agenda.
Subject(s)
Anxiety Disorders/classification , Anxiety Disorders/diagnosis , Decision Making , Practice Guidelines as Topic , Evidence-Based Medicine , Humans , International Classification of Diseases , Severity of Illness Index , Treatment OutcomeABSTRACT
BACKGROUND: Psychiatric classification based on clinical judgement is not very reliable. Reliability can be increased by the use of standardised interviews. Maximum standardisation of the classification process can both improve reliability and affect treatment. AIM: To determine the effect that the use of a highly standardised and automated classification procedure (MiniScan) can have on the length of stay in hospital and on the course of symptoms. METHODS: Participants were allocated to a test group and a control group. The test group was classified via the MiniScan, the control group on the basis of clinical judgement. Length of hospital stay and symptom course were determined. RESULTS: The use of the MiniScan had no effect on the length of hospital stay, but seemed to play a role in symptom reduction. CONCLUSION: There are indications that the use of the MiniScan contributes to symptom reduction.
Subject(s)
Length of Stay , Mental Disorders/classification , Mental Disorders/diagnosis , Psychometrics/standards , Adult , Female , Humans , International Classification of Diseases , Interview, Psychological , Male , Middle Aged , Pilot Projects , Psychiatric Status Rating Scales , Reproducibility of Results , Severity of Illness IndexABSTRACT
BACKGROUND: Borderline personality disorder (BPD) is a frequent and often severely debilitating disorder. According to the definition, a personality disorder is stable and of long duration. In the last few years, however, more and more research results have demonstrated improvements in patients with bpd and even remission. AIM: To investigate to what extent the diagnosis of bpd is stable over time. METHOD: The literature was reviewed systematically with the help of Medline, PsycINFO, EMBASE and the Cochrane Library. RESULTS: After 10 years 88% of adults originally diagnosed as having BPD failed to meet the DSM-IV criteria. Of the various symptoms the affective ones seemed to be the most stable and the impulsive ones the least stable. All symptoms were significantly less severe. With regard to psychosocial functioning, improvements occurred more slowly. Dysfunctioning in relationships was the most stable. It is not clear whether impairments in functioning will persist. CONCLUSION: In recent years there has been a considerable amount of prospective research into the stability of the diagnosis of BPD. Results show that the prognosis relating to symptom reduction and psychosocial functioning is much more favourable than previously assumed.
Subject(s)
Borderline Personality Disorder , Internal-External Control , Adult , Borderline Personality Disorder/diagnosis , Borderline Personality Disorder/epidemiology , Borderline Personality Disorder/psychology , Female , Humans , Interpersonal Relations , Male , Prognosis , Psychometrics , Remission InductionABSTRACT
Differentiating panic disorder form epilepsy can be a difficult task. In this case study the task was made more complicated because the patient was being treated with the selective serotonin reuptake inhibitor (SSRI) citalopram which evoked a partial response, thereby delaying the diagnosis of epilepsy. Research results demonstrate that ssris can have not only an antidepressive and calming effect, they can also have an anticonvulsant effect. However, there are also signs that, as this case illustrates, in the long term the anticonvulsant effect can actually convert to proconvulsant effect.
Subject(s)
Citalopram/adverse effects , Epilepsy/diagnosis , Panic Disorder/diagnosis , Selective Serotonin Reuptake Inhibitors/adverse effects , Adult , Citalopram/therapeutic use , Diagnosis, Differential , Humans , Male , Panic Disorder/drug therapy , Selective Serotonin Reuptake Inhibitors/therapeutic useABSTRACT
Both Parkinson's disease and its treatment can be associated with psychiatric symptoms. We illustrate this link by focusing on a patient suffering from Parkinson's who received not only deep brain stimulation but also excessive amounts of dopaminergic drugs, a combination that resulted in hypomania which is also known as dopamine dysregulation syndrome. We discuss the symptoms, possible aetiological pathways and the implications for clinical practice.
Subject(s)
Antiparkinson Agents/adverse effects , Dopamine Agents/adverse effects , Mood Disorders/chemically induced , Parkinson Disease/drug therapy , Adult , Antiparkinson Agents/therapeutic use , Contraindications , Deep Brain Stimulation , Dopamine/metabolism , Dopamine Agents/therapeutic use , Humans , Iatrogenic Disease , Male , Mood Disorders/diagnosis , Parkinson Disease/psychology , SyndromeABSTRACT
BACKGROUND: Ever since the first descriptions of obsessive-compulsive disorder (ocd) there have been discussions about how the phenomenology of the disorder should be understood. Over the past 50 years the main emphasis has been on the phobic elements of ocd. A new psychological model, called the Inference Based Approach (iba), focuses on an underexposed aspect of the disorder, namely the strange convictions of the patient. AIM: To compare the new model with the existing cognitive behavioral theories of ocd. METHOD: Literature research was conducted using Medline. RESULTS: According to the iba it is assumed that patients with ocd feel anxious because their testing of reality is imperfect. Patients would not feel any anxiety if they were able to integrate adequately information obtained via their senses. In that case ocd would be a cognitive disorder, not an anxiety disorder. Although the model provides an attractive explanation for the symptoms of ocd and some of the research results seem to support the model, many questions still remain unanswered. CONCLUSION: There are indications that, at least in some ocd patients, anxiety might be only a part of the disorder rather than the core.
Subject(s)
Anxiety Disorders/psychology , Cognition Disorders/psychology , Models, Psychological , Obsessive-Compulsive Disorder/psychology , Compulsive Behavior/psychology , Humans , Obsessive Behavior/psychologyABSTRACT
BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders in adults and the elderly. For adolescents however, ect is still a controversial treatment because little research has been done into the efficacy and side effects of ECT in adolescents and because psychiatrists working with children and adolescents are relatively unfamiliar with this form of treatment. AIM: To investigate the efficacy of ECT in adolescents who were treated in Meerkanten between 2000 and 2006 for a therapy-resistant depressive episode and/or suicidal behaviour. METHOD: Scores on the Hamilton Depression Rating Scale or the Montgomery-Asberg Depression Rating Scale before and after ECT were compared. The percentage improvement on the depression scales and the percentage of patients who showed an improvement of at least 60% on the scales in the group of adolescents were compared with the percentage improvement in a group of adults treated in Meerkanten. RESULTS: One-third of the adolescent patients showed an improvement of 60% or more on these scales; the average improvement was 46%. ECT was found to be equally effective in adolescents and adults. CONCLUSION: ECT is a successful form of treatment for one-third of adolescents with a severe therapy-resistant depressive episode; this is a clinically relevant result for these patients for whom no alternative treatments are available.
Subject(s)
Depressive Disorder/therapy , Electroconvulsive Therapy/methods , Adolescent , Electroconvulsive Therapy/adverse effects , Female , Humans , Male , Psychiatric Status Rating Scales , Retrospective Studies , Severity of Illness Index , Treatment OutcomeABSTRACT
Two patients, young women aged 15 and 17, both suffering from major depression with psychotic features, were resistant to treatment with antidepressive regimen and psychotherapy. Both patients became severely suicidal and were subsequently successfully treated with electroconvulsive therapy (ECT). The second patient needed maintenance ECT once a month in order to stay in remission. Whereas ECT is a well-studied and accepted treatment option in adult psychiatry, in child psychiatry people are reluctant to even consider this option. This resistance is partly based on the possible side effects ofECT i.e. memory problems. As a result, the effect ofECT in adolescents has not yet been well studied. In 2004, the American Academy of Child and Adolescent Psychiatry proposed guidelines for the use of ECT in adolescents. Following these guidelines, the use ofECT in adolescents seems to be a safe treatment option, however further research to the effect of ECT in this age group is warranted.
Subject(s)
Depressive Disorder, Major/therapy , Electroconvulsive Therapy , Psychotic Disorders/therapy , Adolescent , Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Electroconvulsive Therapy/adverse effects , Female , Humans , Psychotherapy , Psychotic Disorders/drug therapy , Remission Induction , Suicidal Ideation , Treatment OutcomeABSTRACT
RATIONALE: Antidepressants may vary widely in their potential to impair cognitive and psychomotor functions. Little is known about their effects on event-related brain potentials (ERPs).OBJECTIVES. To compare the effects of three pharmacologically different antidepressants on performance and ERPs in tasks of selective attention and working memory. METHODS: Subjects were treated for 8 days with amitriptyline (sedative/anticholinergic TCA), nefazodone (5-HT(2) receptor antagonist), paroxetine (SSRI) and placebo, in a double-blind, crossover design. Measurements were carried out on day 1 and 8 of each treatment period. A task was used in which memory load (two and four items) and attention (focused, divided) were orthogonally varied. RESULTS: On day 1 amitriptyline increased reaction times (focused attention) and the percentage of misses (load 4>load 2) and false alarms. Sensitivity (A') was reduced as a function of memory load. Effects were greatly diminished on day 8. The ERP analysis yielded a reduced early frontal positive difference wave related to memory load (day 1). Attention-related search negativity was slightly prolonged. P3 latency (stimulus evaluation time) was prolonged. P3 amplitude was reduced (mainly on day 8) suggesting diminished attention capacity. Nefazodone increased reaction times and miss rates and reduced sensitivity (A') on day 8 only. Paroxetine speeded responses on day 1 and slightly increased miss rates on day 8. Performance effects of nefazodone and paroxetine did not interact with the task factors. Search negativity and P3 measures were not affected. CONCLUSIONS: The results suggest that the pharmacologically selective serotonergic antidepressants lack the specific memory and attention deficits seen with amitriptyline. Both performance and ERP data suggest that paroxetine and nefazodone may influence response-related processes, while for nefazodone an effect on other processes cannot be excluded.
Subject(s)
Antidepressive Agents/pharmacology , Attention/drug effects , Memory/drug effects , Adult , Amitriptyline/pharmacology , Cross-Over Studies , Double-Blind Method , Drug Administration Schedule , Electroencephalography , Electrooculography , Evoked Potentials/drug effects , Evoked Potentials/physiology , Female , Humans , Male , Neuropsychological Tests , Paroxetine/pharmacology , Piperazines , Reaction Time , Task Performance and Analysis , Triazoles/pharmacologyABSTRACT
OBJECTIVE: To determine the adequacy of drug treatment for patients with obsessive compulsive disorder (OCD). DESIGN: Retrospective. METHOD: One hundred and fifty outpatients with OCD, admitted at the University Medical Centre in Utrecht, the Netherlands, were evaluated for severity as measured with the 'Yale-Brown obsessive compulsive scale' (Y-BOCS). RESULTS: At the intake, 35% of the patients used no medication, 58% used an antidepressant, less than 1% an antipsychotic and 6% a benzodiazepine. The average active dose was taken by 12% of the patients, 5% took the maximum dosage and 41% too low a dosage. Consequently, 6 out of the 10 patients used the correct medication (antidepressant) and less than 20% used a sufficiently high dosage. Of the patients, 38% had never previously taken antidepressants, 31% had previously used one antidepressant, 17% two different antidepressants and 12% at least three different antidepressants; 13% had taken the antidepressant at the highest dosage, 18% at the average active dosage and 31% at too low (thus ineffective) a dosage. This means that from a pharmacotherapeutic viewpoint not more than 1 in 8 patients had had an adequate treatment history. CONCLUSION: The results of this study show that only 1 in 8 OCD patients were treated appropriately.
Subject(s)
Anti-Anxiety Agents/administration & dosage , Antidepressive Agents/administration & dosage , Drug Utilization/statistics & numerical data , Medication Errors/statistics & numerical data , Obsessive-Compulsive Disorder/drug therapy , Adult , Benzodiazepines , Dose-Response Relationship, Drug , Drug Prescriptions/statistics & numerical data , Drug Therapy, Combination , Drug Utilization/standards , Female , Humans , Incidence , Male , Middle Aged , Netherlands/epidemiology , Outpatients/statistics & numerical data , Retrospective Studies , Utilization ReviewABSTRACT
The non-selective serotonin (5-HT) receptor agonist meta-chlorophenylpiperazine (mCPP) has been reported to elicit symptoms in patients with obsessive compulsive disorder (OCD). MK-212, another non-selective 5-HT receptor agonist, does not seem to induce obsessive compulsive symptoms in OCD patients. The major pharmacological difference between mCPP and MK-212 is their affinity for the 5-HT(ID) receptor. The aim of this study was to explore the role of the 5-HT(ID) receptor in the pathophysiology of OCD, by using a challenge paradigm with the selective 5-HT(ID) receptor agonist sumatriptan (Imigran). A randomized, double-blind, placebo-controlled crossover challenge with sumatriptan (100 mg PO) was performed in 15 OCD patients. Neither the obsessive compulsive symptoms nor mood or anxiety symptoms changed significantly following sumatriptan administration as compared to placebo. Sumatriptan did induce a significant increase in plasma growth hormone (GH) levels. In the present study, no indication were found for the role of the 5-HT(ID) receptor in the pathophysiology of OCD. It should be noted, however, that sumatriptan does not readily pass the blood-brain barrier. Selective 5-HT(ID) receptors with better brain penetrating properties may shed more light on the role of this 5-HT receptor subtype in OCD.
Subject(s)
Obsessive-Compulsive Disorder/physiopathology , Sumatriptan/blood , Sumatriptan/pharmacology , Adolescent , Adult , Analysis of Variance , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Middle Aged , Serotonin Receptor Agonists/pharmacologyABSTRACT
Data from animal studies suggest a functional relationship between the cholecystokinin-ergic (CCK) and the serotonergic (5-HT) system. There is increasing evidence that the cholecystokinin-4 (CCK4) challenge test could be a valid experimental model for panic attacks in man. The aim of the present study is twofold; 1) to validate this model further and 2) to shed more light on the putative CCK/5-HT interaction. To this end, we studied the effect of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine on CCK4-induced panic attacks. Twenty-six panic disorder (PD) patients received, before and after a double blind 8-week treatment period with fluvoxamine (n = 17) or placebo (n = 9), a single blind bolus injection with 50 micrograms CCK4. Treatment with fluvoxamine (150 mg daily) significantly decreased the sensitivity of PD patients for CCK4 while placebo was without effect. Of the patients who responded to treatment, 83% no longer experienced a panic attack when rechallenged with CCK4, whereas in the non-responders group this was only 28%. In the fluvoxamine group the treatment response evaluated by the Hamilton Anxiety Scale (HAS) showed a statistically significant treatment effect. The results of this study strengthen the validity of the CCK4 test as an experimental human model for panic attacks and yield evidence supporting the hypothesis that both CCK and serotonin are implicated in the regulation of anxiety.
Subject(s)
Fluvoxamine/pharmacology , Panic Disorder/chemically induced , Tetragastrin/pharmacology , Adult , Female , Humans , Male , Models, Psychological , Neuropsychological TestsABSTRACT
The effects of the cholecystokinin-B (CCK-B) receptor antagonist CI-988 on symptoms elicited by the cholecystokinin tetrapeptide (CCK4) were studied in DSM-IIIR patients with panic disorder. The study employed a double-blind, two-period incomplete block design. Patients (n = 14) received two different dosages of CI-988 (50 mg or 100 mg) or placebo 2 h prior to an IV bolus injection of CCK4 (20 micrograms) on two separate occasions. The primary efficacy parameter was the total intensity score on the Panic Symptoms Scale (PSS). Secondary parameters were the number of panic symptoms, time to and occurrence of the first panic symptoms, duration of symptoms, intensity of apprehension and the percentage of patients who did not have a panic attack. The PSS failed to show a statistically significant treatment effect on any of these outcome measures. The average panic rate was 50%, 14.3% and 37.5% after placebo, 50 and 100 mg CI-988, respectively. The differences in panic rate were not statistically significant. The results of this study suggest that CI-988 in doses up to 100 mg is not effective in reducing symptoms of panic anxiety induced by CCK4.
Subject(s)
Anti-Anxiety Agents/therapeutic use , Indoles/therapeutic use , Meglumine/analogs & derivatives , Panic Disorder/drug therapy , Receptors, Cholecystokinin/antagonists & inhibitors , Adolescent , Adult , Anti-Anxiety Agents/blood , Cross-Over Studies , Double-Blind Method , Female , Humans , Hydrocortisone/blood , Indoles/blood , Male , Meglumine/blood , Meglumine/therapeutic use , Middle Aged , Panic Disorder/chemically induced , Receptor, Cholecystokinin B , Tetragastrin , Treatment OutcomeABSTRACT
Cholecystokinin (CCK) plays an important role in both the alimentary tract and the central nervous system (CNS). At present it seems to be the most abundant neuropeptide in the CNS. This paper reviews the CCK neuronal system and its interactions with gamma-aminobutyric acid (GABA) and serotonin (5-hydroxytryptamine; 5-HT). In addition, its putative role in anxiety will be discussed on the basis of animal data and studies in healthy volunteers and panic disorder patients. According to these investigations, the CCK4 challenge test fulfills most criteria for an ideal panicogenic agent and evidence has been found that CCKB receptor antagonists might possess anxiolytic properties in man.
Subject(s)
Anxiety/metabolism , Cholecystokinin/metabolism , Animals , Humans , MaleSubject(s)
Agoraphobia/drug therapy , Benzodiazepinones/pharmacology , Lactic Acid , Panic Disorder/drug therapy , Phenylurea Compounds , Receptors, Cholecystokinin/antagonists & inhibitors , Adult , Agoraphobia/diagnosis , Agoraphobia/psychology , Arousal/drug effects , Double-Blind Method , Female , Humans , Male , Middle Aged , Pain Measurement , Panic Disorder/diagnosis , Panic Disorder/psychology , Receptor, Cholecystokinin B , Receptors, Cholecystokinin/physiologyABSTRACT
We studied the effect of the cholecystokinin tetrapeptide (CCK4), a potent CCKB antagonist, in patients with panic disorder. Two different dosages (25 and 50 micrograms) of CCK4 and saline were tested in 12 patients who were randomly allocated to 2 of the 3 possible treatment groups. Patients were tested on 2 separate occasions, 1 week apart, using an unbalanced single-blind incomplete block design. A total of 24 intravenous injections were carried out. The panic rate with 25 micrograms CCK was 44% (4/9) and 71% (5/7) with 50 micrograms. None of the patients panicked with saline (0/8). Patients' symptom responses were very similar to their spontaneous panic attacks. Taking the Panic Symptom Scale (PSS) as outcome variable, we found that CCK4 provoked symptoms of panic in a dose-dependent fashion. The behavioral response to CCK4 was not accompanied by activation of the hypothalamic-pituitary-adrenal (HPA) axis as measured by the prolactin and cortisol responses. Moreover, CCK4-induced panic symptoms were not correlated with plasma increases in the principal noradrenergic metabolite, 3-methoxy-4-hydroxy-phenylglycol (MHPG), suggesting that activation of the locus coeruleus may not be critical for CCK4-induced panic.
Subject(s)
Panic Disorder/drug therapy , Tetragastrin/pharmacology , Adult , Dose-Response Relationship, Drug , Female , Humans , Male , Methoxyhydroxyphenylglycol/metabolism , Middle AgedABSTRACT
In the present open study the effects of the D1-dopamine antagonist SCH 39166 on positive and negative symptoms of schizophrenia (DSM-IIIR) were investigated. SCH 39166 was given orally according to a fixed dosage schedule (day 1: 25 mg b.i.d; day 4: 50 mg b.i.d.; day 7: 100 mg b.i.d.; day 18: 200 mg b.i.d.; day 21: 225 mg b.i.d.). Seven patients completed 2 weeks, and five patients completed the study. The reason for premature withdrawal was lack of efficacy or refusal to take SCH 39166. In none of the patients a reduction of the BPRS or CGI score was found. As measured with the PANSS, a significant reduction was observed in the score of the negative subscale, whereas the positive symptoms scale and general psychopathology score remained unaffected. Akathisia, rigidity and hypokinesia were reported occasionally, although only mild in severity. The results of the present study do not support the hypothesis that D1-dopamine antagonists are clinically effective antipsychotics in schizophrenia, considering the fact that SCH 39166 had no effect on positive symptoms. The present study provides circumstantial evidence for an effect of SCH 39166 on negative symptoms.
