Differential depression and organic disorder diagnosis and their possible treatments

This paper deals with an important differential diagnosis of depression. While mood disorders are more and more subclassified in present days, the clinically very similar psychopathological pictures, produced by "disturbances due to a general medical condition" (DSM-IV) evokes less and less interest. Misdiagnosis may lead to antidepressant therapy, which will not be well tolerated by the patient. Therefore the symptomatology of acute and chronic, diffuse and localized brain disturbances is outlined for easy clinical use.     

Neuroleptic-induced acute extrapyramidal syndromes and tardive dyskinesia

Neuroleptic drug-induced acute extrapyramidal symptoms and later-onset tardive dyskinesia are major limitations to these valuable drugs. Each of these disorders can be described by special risk factors that include patient characteristics, drug factors, and temporal considerations. The limitations that derive from these motor side effects have been one of the major reasons propelling the search for neuroleptic drugs that are free of these side effects. Strategies for managing the acute and late-onset extrapyramidal syndromes are presented. Significantly more research is needed, however, on all these disorders before a unified and cohesive explanation can account for these seemingly disparate syndromes. New medications, which effectively treat schizophrenia and are free of acute extrapyramidal syndromes and tardive dyskinesia, will be a giant step forward in patient care and our knowledge of the mechanisms controlling both mental function and motor control.     

The interdisciplinary team''s approach to lupus nephritis

BACKGROUND: Animal and postmortem studies indicate that neuroleptic therapy may induce D2 dopamine receptor up-regulation in the basal ganglia. METHODS: To address this phenomenon in a clinical study, we investigated the D2 dopamine receptor binding in 15 DSM-III-R schizophrenics in the drug-naive state and 3 days after completion of a standardized neuroleptic therapy (benperidol 12-16 mg/day, for 25 days) using single photon emission computed tomography (SPECT). SPECT scans were obtained 2 hours after intravenous injection of 185 MBq 123I-iodobenzamide. For analysis, basal ganglia to frontal cortex (BG/FC) ratios were calculated and the patient sample was subgrouped into patients with a favorable versus a poor treatment response. RESULTS: Neuroleptic treatment led to decreased BG/FC ratios in patients with a favorable response, but increased ratios in the poor responders (df = 1, F = 4.1, p = .06). Changes of BG/FC ratios were significantly correlated with extrapyramidal side effects but not with neurological soft signs. CONCLUSIONS: Our findings suggest that neuroleptic therapy may induce D2 dopamine receptor up-regulation in a subgroup of patients characterized by poor treatment response and pronounced extrapyramidal side effects.     

The ralationship between changes in 5-HT induced platelet aggregation and clinical state in patients treated with fluphenazine

Platelet aggregation responses to 5-HT and adenosine diphosphate were examined in a population of eighteen patients treated with fluphenazine decanoate for longer than one year. 5-HT induced aggregation was enhanced in ten subjects. This enhancement was similar to that previously described in patients receiving chlorpromazine. Patients who showed enhanced 5-HT induced aggregation showed less rateable psychopathology and less extrapyramidal side-effects than patients who did not show enhancement. These findings suggest that platelet aggregation responses could be used to identify patients who could be safely withdrawn from long-term neuroleptic therapy.     

Non-genomic action of steroids in the nervous system

Past research on the importance of 'soft' neurological signs in schizophrenia has often not examined the relationship between specific groups of neurological signs and different dimensions of schizophrenia psychopathology. Gender differences in the reported relationships have never been explored. In this paper we describe a study of 100 DSM-III-R (65 male and 35 female) schizophrenic patients who were rated for neurological 'soft signs' with the Neurological Evaluation Scale (NES) (1), and for schizophrenic symptomatology with the Scale for Assessment of Negative Symptoms (SANS) and the Scale for Assessment of Positive Symptoms (SAPS). Following a factor analysis of NES items, differential relationships were examined between the five derived NES factors and three well-established dimensions of schizophrenic symptomatology, namely psychomotor poverty, disorganization and reality distortion. Our results failed to show any relationship between NES dimensions and either the reality distortion or disorganization dimensions. There was a modest but differentially significant relationship between psychomotor poverty and an extrapyramidal factor on the NES. This relationship was shown only by male subjects, and was influenced by duration of illness but not by age or neuroleptic medication. On the other hand, female subjects showed a significant relationship between psychomotor poverty and an NES factor reflecting attention and initiative, and between reality distortion and coordination/sequencing of motor activity. These relationships in female subjects were, relative to relationships for male subjects, more independent of the effect of medication and duration of illness.     

Bilateral striatal lesions in childhood

From 1983 to 1991, 13 patients were identified with a clinical radiologic association characterized by acute or persistent neurologic dysfunction and bilateral lesions in the basal ganglia region demonstrated by ultrasound, computed tomography, or magnetic resonance imaging. Initial clinical manifestations of this group of patients were characterized by extrapyramidal signs (i.e., dystonia 9, hypotonia 2, athetosis 1, rigidity 1), altered state of consciousness in 5, and seizures in 3. The outcomes of most of these patients were poor: 10 had motor sequelae, 9 cognitive impairment, and 4 died. The outcomes of 2 patients, however, were much better than what was expected from the initial presentation. Based on current and previous reports, the diagnostic approach and classification of patients with neurologic dysfunction and bilateral striatal lesions are presented.     

Dextromethorphan phenotyping and haloperidol disposition in schizophrenic patients

This study examined the relationship between the metabolic ratios of dextromethorphan/dextrorphan, haloperidol disposition, and the incidence of extrapyramidal side effects in schizophrenic patients. Eighteen schizophrenic patients were phenotyped with a test dose of dextromethorphan prior to the initiation of haloperidol treatment. The metabolic ratio of dextromethorphan/dextrorphan was determined in each patient. Patients were treated with oral haloperidol 10 mg/day for 2 weeks. Blood samples for haloperidol and reduced haloperidol were obtained at week 2 of haloperidol treatment. Haloperidol and reduced haloperidol plasma concentrations were assayed by HPLC with electrochemical detection. Significant correlations of dextromethorphan/dextrorphan metabolic ratios vs. plasma haloperidol concentrations, reduced haloperidol concentrations, and reduced haloperidol/haloperidol ratios were found (r = 0.726, P = 0.0007; r = 0.782, P = 0.0001; and r = 0.619, P = 0.006, respectively). Ten patients who experienced extrapyramidal side effects had higher reduced haloperidol concentrations and reduced haloperidol/haloperidol ratios than the other patients (2.49 +/- 1.42 [S.D.] ng/ml vs. 1.10 +/- 0.46 ng/ml, P = 0.014 and 0.287 +/- 0.102 vs. 0.192 +/- 0.065, P = 0.030). The former also had a trend to have higher haloperidol concentrations and dextromethorphan/dextrorphan ratios than the latter (8.04 +/- 2.91 ng/ml vs. 5.83 +/- 1.79 ng/ml, P = 0.066 and 0.023 +/- 0.017 vs. 0.011 +/- 0.010, P = 0.077). Phenotyping patients has the potential to assist clinicians in predicting plasma drug concentrations during the subsequent neuroleptic drug treatment. Further research with phenotyping and psychotropic drug metabolism in psychiatric patients is needed.     

The effect of the beta-adrenergic blocking agent propranolol in mania (author's transl)

Six patients with the diagnosis of acute mania were treated with high doses of the beta-adrenergic blocking agent propranolol. One of these patients was treated during two manic phases. Psychopathologic change during treatment was rated daily by a psychiatrist not informed on the patients medication. The IMPS (Inpatient Multidimensional Psychiatric Scale) was used. Three cases were placebo-controlled under double blind conditions. Four times we had a second medication period, twice with propranolol and once with oxprenolol and dexpropranolol respectively. Propranolol was administered every 4 h (six times per day), starting with single doses of 20-40 mg. Doses were increased individually under control of pulse rate, blood pressure, and ECG. Augmentation of doses was continued until an effect on manic symptomatology was undoubtedly seen or until therapy had to be discontinued because of side-effects. In four patients definite improvement of manic symptomatology could be achieved during altogether five manic phases within usually two treatment periods of 5-15 days. Manic behavior disappeared completely in two of these patients. The effective dosage of propranolol varied between 280 and 2320 mg per day. All of the improved patients relapsed after discontinuation of the drug. In the only case on dexpropranolol (5 days up to 900 mg daily) the effect was questionable. No extrapyramidal side-effects were observed. In one patient treatment was discontinued because of lack of cooperation, in another because of extrasystoles. Gastrointestinal bleeding occurred in the patient who received dexpropranolol. This complication was possibly due to other medication. Other side-effects were insomnia, hypertension, precordial pain, abdominal pain as well as the expected hypotension and bradycardia. The significance of these results regarding the catecholamine hypothesis of manic-depressive illness is discussed.     

Serum cytokine levels in heart allograft recipients: correlation with findings on endomyocardial biopsy

We report the first double-blind, placebo-controlled continuation study comparison of a neuroleptic (haloperidol < or = 6 mg), monoamine oxidase inhibitor (MAOI) antidepressant (phenelzine < or = 90 mg), and placebo in 54 patients with borderline personality disorder. Continuation medication trials of 16 weeks followed 5 weeks of acute therapy. Haloperidol continued to be effective beyond the acute phase only for the treatment of irritability. Higher levels of depression, hypersomnia, and leaden paralysis were noted in the haloperidol group than in the phenelzine and placebo groups. The dropout rate during the first half (8 weeks) of the continuation study was significantly higher for the haloperidol group (64%) than for the placebo group (28%) (p < .05). Phenelzine demonstrated very modest efficacy beyond that noted in the acute phase for the treatment of depression and irritability. Phenelzine was shown to have an activating effect on measures of excitement and reactivity.     

Psychiatric morbidity and depressive symptomatology in patients with permanent pacemakers

Implantation of a permanent pacemaker requires a psychological effort on the patient's part for adaptation in the acute term, and chronically, it restricts activities of the patient and may cause some psychiatric disturbances. To investigate psychiatric morbidity and depressive symptomatology of the patients with permanent pacemakers, 84 pacemaker patients were diagnosed using the DSM-III-R criteria and depressive symptoms were determined by modified Hamilton Depression Rating Scale (mHDRS). Sixteen (19.1%) patients had been given a psychiatric diagnosis. The most frequent diagnoses were adjustment disorder (5.9%) and major depressive episode (4.7%). Nine patients (10.7%) were diagnosed as having clinical depression (mHDRS > or = 17). The mean score of mHDRS was 7.57 +/- 7.46, and the severity of depression was significantly higher in females. The most frequent symptoms are difficulties in work and activities (53.6%), psychic anxiety (48.8%), loss of energy (42.9%), and hypochondriasis and insomnia (39.3%). Depressed mood, psychic anxiety, loss of energy, loss of interest, insomnia, and hypochondriasis were significantly more frequent in females. Uneducated patients had a more significant loss of energy than educated patients. Depressed mood, psychic anxiety, and somatic concerns and symptoms were more frequent in patients with permanent pacemakers than in the general population. These symptoms, resembling mixed anxiety-depression disorder, were related to fears of having a permanent pacemaker, since our series were composed of uneducated patients who did not have enough knowledge about the device.     

Haloperidol-induced extrapyramidal reaction: lack of protective effect by vitamin E

Haloperidol treatment has been shown to produce oxidative stress in patients with acute psychosis. Oxidative stress has also been implicated in the extrapyramidal symptoms (EPS) produced by haloperidol. Supporting the oxidative stress hypothesis, vitamin E (antioxidant) has demonstrated therapeutic efficacy in idiopathic parkinsonism. The prophylactic efficacy of vitamin E (antioxidant) on haloperidol-induced EPS was examined in a randomized controlled trial. The sample consisted of 24 acute psychotic patients hospitalized for a 2-week trial. All patients received oral haloperidol 10 mg/day. The sample was equally randomized to receive either haloperidol alone or haloperidol + vitamin E (3200 IU/day). EPS was rated at recruitment, both live and with video records, and on days 3, 7, 10 and 14. Psychopathology was rated at recruitment and weekly thereafter. Vitamin E had no prophylactic effect on drug-induced EPS, though it did not interfere with the therapeutic efficacy of haloperidol.     

Akathisia

The syndrome of akathisia typically consists of a subjective component, e.g. inner restlessness and an urge to move, and observable symptoms such as restless legs and inability to sit still. In most cases akathisia is caused by neuroleptics. There are several subtypes of akathisia according to the time of onset in the course of neuroleptic treatment. In clinical routine extrapyramidal motor disturbances are often underestimated or misinterpreted. As far as akathisia is concerned, differential diagnosis of restlessness or of repetitive movement patterns may be problematic. Non-compliance and impulsive behaviour are regarded as possible complications of akathisia, but systematic investigations are lacking. The pathophysiology of akathisia is not clear, but it probably differs from other pharmacologically induced motor disturbances. If warrantable, the first step in akathisia treatment is dose-reduction of the causing agent. Anticholinergic drugs, benzodiazepines, and beta-receptor blockers may be effective. Clinical assessment and survey of the patient's behaviour, e.g. during occupational therapy and group therapy is important for an early diagnosis of akathisia so that complications may be minimised.     

Incidence of extrapyramidal syndromes in AIDS patients and a comparison group of medically ill inpatients

The authors retrospectively reviewed the charts of 29 inpatients with AIDS and 24 medically ill inpatients, all of whom were exposed to neuroleptics. Results adjusted for age, gender, type and dosage of neuroleptic, and extrapyramidal prophylaxis indicated that inpatients with AIDS were 7 times more likely to develop extrapyramidal syndromes (EPS) from neuroleptics than the comparison group of medically ill inpatients. Possible neuroanatomic, neuropathologic, and neurochemical reasons for the vulnerability of patients with AIDS to EPS are reviewed.     

Asthenic disorders in burn disease

A total of 73 patients with burn disease were examined. The whole period of the disease was marked by a distinct asthenic symptomatology shown by predominance of physical asthenia, by stable and stereotypic mental disturbances. The asthenic disorders correlated with the somatic state of the patient. Such disorders were seen for a long period of time, and even after recovery. Apart from asthenic symptomatology, all the patients demonstrated disturbances in the intellectual sphere, and in intellectual-mnestic processes, which were also seen in the late periods of burn disease. The changes in the neurologic state were characterized by lesions of the cranial nerves, anizoreflexia of the hemitype, pathological reflexes in the hand and feet, vegetative-trophic disturbances indicating that all the patients who had extensive and deep burns developed encephalopathy.     

Neuroleptic treatment increases soluble IL-2 receptors and decreases soluble IL-6 receptors in schizophrenia

The cytokines interleukin-2 (IL-2) and interleukin-6 (IL-6) increase during immune activation, they are released from activated astrocytes and microglial cells in the central nervous system (CNS), and they are able to enhance the catecholaminergic neurotransmission. This study focused on the soluble receptors of IL-2 and IL-6 (sIL-2R, sIL-6R) as a part of the regulation system of IL-2 and IL-6. We studied serum levels of sIL-2R in 30 schizophrenic patients not under neuroleptic medication during an acute exacerbation of the disease and reexamined these patients under neuroleptic treatment after clinical improvement. The sIL-6R levels of 39 schizophrenic patients were estimated under the same conditions. The results were compared with the levels of sIL-2R and sIL-6R in 42 healthy controls. No difference was found between the schizophrenic patients before neuroleptic treatment and the healthy controls. During neuroleptic treatment, however, there was a significant increase of sIL-2R levels and a significant decrease of the sIL-6R levels between the pre- and post-conditions. In comparison with healthy controls, the treatment group also showed increased sIL-2R levels and decreased sIL-6R levels. These results suggest that treatment with neuroleptics is associated with increased sIL-2R and decreased sIL-6R. Since sIL-2R bind and inactivate IL-2, whereas sIL-6R form an active complex with IL-6, the increase of sIL-2R and the decrease of sIL-6R together may reflect a functional down regulation of these activating cytokines. This suggests that neuroleptic therapy has a differentiated immunomodulatory effect.     

Neuroleptic dosing in Hispanic and Asian Inpatients with schizophrenia

This study is the second in a series examining the prescribing of antipsychotic medication to patients with schizophrenia in cross-cultural clinical programs. A computer search identified all patients with the diagnosis of "schizophrenia" treated during a 1-year period in an inpatient Hispanic and Asian psychiatric unit(s); second computer search identified a matched (admission date) sample of Anglo patients from the general inpatient psychiatry services. The medication variables included type of neuroleptic drug used, the maximum dose, the stabilized dose (i.e., neuroleptic dose at discharged and the dose associated with first report of extrapyramidal symptoms. Neuroleptic doses were converted to chlorpromazine (CPZ) equivalents and corrected for body weight to a standard of 68 kg. Oneway analysis of variance procedures were used to compare both actual and standardized neuroleptic CPZ across the three samples, these statistical comparisons were completed for both maximum and stabilized dose(s). The analysis with maximum dose revealed a significant main effect for both actual (p < 0.05) and standardized CPZ (p < 0.05). Similar results were also found for stabilized dose with both actual (p < 0.05) and standardized CPZ (p < 0.05). Examination of the direction of mean differences for both medication dosing variables using both CPZ comparisons revealed that the patients in general sample received significantly larger doses of antipsychotic medication than either Asian or Hispanic patients.     

Remission of schizophrenic psychosis with negative symptoms with risperidone

The appearence of extrapyramidal motor disorders and the inadequate response of the negative symptoms to classical neuroleptic treatment represent a serious impairment for the patient that make rehabilitation and reintegration into the work setting difficult or even impossible. Such patients can profit from a changeover to risperidone, which has a more favorable side effects profile and an appreciably better effect on the negative symptoms than classical neuroleptics. The therapeutic usefulness of risperidone treatment is illustrated by the case of a 27-year-old technician whose pronounced negative symptoms failed to respond to classical neuroleptic treatment.     

Dose-response relationships for the antipsychotic effects and Parkinsonian side-effects of typical neuroleptic drugs: practical and theoretical implications

1. From a review of published literature it is concluded that the minimum dose of a neuroleptic drug (NLD) required to alleviate psychosis is very similar to that producing minimal parkinsonian side effects (PSE). This conclusion is reached both from group comparisons and individual comparisons of dose/response relations (DRR) for the two effects. 2. A lower dose of NLD is usually sufficient to prevent relapse in well stabilized patients than is needed to check an active psychotic state. 3. Anticholinergic agents used to reduce side effects of typical NLD can retard the therapeutic process during neuroleptic treatment of acute psychosis. Although it is not fully established that this is a central interaction, it is consistent with the idea that minimal side effects are a necessary condition for therapeutic effectiveness with typical antipsychotic drugs. 4. In relapse-free maintenance of psychosis-prone patients, tolerance occurs to PSE. Thus few patients need experience prolonged side effects during maintenance treatment with neuroleptics. 5. The evidence reviewed is discussed with respect to a previous hypothesis of the supposedly "indirect" action of typical neuroleptic drugs in therapy for psychosis. The evidence is consistent with the idea of a close causal relation between minimal PSE of these drugs, and their therapeutic effectiveness in the acute stage of treatment.     

Response to cognitive therapy in depression: The role of maladaptive beliefs and personality disorders.

This study examined whether personality disorder status and beliefs that characterize personality disorders affect response to cognitive therapy. In a naturalistic study, 162 depressed outpatients with and without a personality disorder were followed over the course of cognitive therapy. As would be hypothesized by cognitive theory (A. T. Beck & A. Freeman, 1990), it was not personality disorder status but rather maladaptive avoidant and paranoid beliefs that predicted variance in outcome. However, pre- to posttherapy comparisons suggested that although patients with or without comorbidity respond comparably to "real-world" cognitive therapy, they report more severe depressive symptomatology at intake and more residual symptoms at termination. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correlation of positive symptoms exclusively to hyperperfusion or hypoperfusion of cerebral cortex in never-treated schizophrenics

BACKGROUND: Studies of schizophrenia by single photon emission computed tomography (SPECT) and positron emission tomography (PET) have shown both regional cerebral hyperperfusion and hypoperfusion. The aim of this study was to examine the inter-relations between regional cerebral blood flow (rCBF), psychopathology, and effects of neuroleptic therapy. METHODS: 24 never-treated patients with acute schizophrenia were examined with hexamethylpropyleneamine-oxime brain SPECT and assessed psychopathologically according to the positive and negative syndrome scale; they were studied again after neuroleptic treatment and psychopathological remission. rCBF values that deviated from those of 20 controls by more than 2 SD were regarded as abnormal. FINDINGS: Both hyperperfused and hypoperfused patterns were found among schizophrenia patients during acute illness. The seven positive symptoms on the symptom scale showed different correlations with rCBF: formal thought disorders and grandiosity correlated positively (and strongly) with bifrontal and bitemporal rCBF; delusions, hallucinations, and distrust correlated negatively (and strongly) with cingulate, left thalamic, left frontal, and left temporal rCBF. Stereotyped ideas as a negative symptom correlated negatively (and strongly) with left frontal, cingulate, left temporal, and left parietal rCBF. After neuroleptic treatment (and reduction of positive symptoms), only negative symptoms correlated exclusively with bifrontal, bitemporal, cingulate, basal ganglia, and thalamic hypoperfusion. INTERPRETATION: Different positive symptoms are accompanied by different rCBF values--some related to hyperperfusion, others to hypoperfusion. This finding may help to explain observed inconsistencies of perfusion patterns in drug-na?ve schizophrenics.