PSYCHOSURGERY—Present Indications and Future Prospects

Although the advent and widespread use of ataractic drugs has more or less eclipsed lobotomy as a method of dealing with severe psychotic states, variations and adaptations of the operation still can be used with benefit in certain pretty well defined circumstances.“Chemical lobotomy” and regressive electroshock bring about alterations in behavior superficially resembling those of lobotomy, but without the changes in personality that are the object of lobotomy. These desirable changes consist in increased extraversion, decreased preoccupation with self and decreased sensitivity to the opinions of others. With restricted operations, undesirable changes—the “frontal lobe syndrome”—do not occur.Operative failures are due to three main causes: (a) Preoperative emotional deterioration; (b) progress of the underlying disease; (c) relapse, possibly due to inadequate operation.Lobotomy is advisable if the patient does not show sustained improvement after a year of active treatment by other indicated means. The operation often represents the turning point in effective treatment. After the first year of ineffective treatment valuable time is being lost, with danger of fixation and deterioration. Then it is safer to operate than to wait.The future of psychosurgery lies in prompt application, in favorable patients, of selective operations that will reverse the trend of illness.There is particular need for further exploration of the temporal lobes in the hope of finding some procedure that will suppress hallucinations. Some 90 per cent of patients remaining in hospitals after psychosurgery are experiencing hallucinations. If these phenomena can be eliminated without producing serious personality defects, another large field for the application of psychosurgery will be opened.     

The Lobotomy Patient—A Decade Later: A Follow-up Study of a Research Project Started in 1948

One hundred and fifty patients with chronic mental illness were treated with prefrontal lobotomy between 1948 and 1952 as part of a research study. Follow-up assessments were made by the author in 1952 and again in 1962. One hundred and sixteen patients of the original 150 were available for the follow-up study which provides the basis for this report. Sixty-seven per cent improved sufficiently to live out of hospital, although 26% did have periods of relapse requiring further treatment. The maximum postoperative response usually occurred at six months and was usually maintained subsequently. Most significant complications of lobotomy were epilepsy (12%) and a personality defect (91%). The results of this lobotomy study were examined in relationship to current psychiatric therapy, with particular reference to recent clinical experience with lobotomy. It was concluded that if prefrontal lobotomy is used for selected cases of intractable mental disorder only, it has probably found its proper place in psychiatric treatment.     

The Gold-Plated Leucotomy Standard and Deep Brain Stimulation

Walter Freeman, the self styled neurosurgeon, became famous (or infamous) for psychosurgery. The operation of frontal leucotomy swept through the world (with Freeman himself performing something like 18,000 cases) but it has tainted the whole idea of psychosurgery down to the present era. Modes of psychosurgery such as Deep Brain Stimulation and other highly selective neurosurgical procedures for neurological and psychiatric conditions are in ever-increasing use in current practice. The new, more exciting techniques are based in a widely held philosophical position on the relationship between the mind, brain and soul, which is the key to ethical debates in this area. Psychosurgery has always posed questions of responsibility, personality, character, identity, spirit, relationship, integrity, and human flourishing and they do not go away when we enter the brave new world of neuroethics and Deep Brain Stimulation.     

Transorbital lobotomy; its use in relapsing psychotic states

Twenty-five private patients were treated by transorbital lobotomy. The period of observation after operation was from six months to three years. In 14 cases of affective disorders in which there was not adequate response to shock therapy, nine patients made social recovery and maintained good health and four were improved. Some follow-up shock therapy was necessary for about one-fifth of the patients. Of eight schizophrenic patients four made excellent social recoveries, two improved and two were not improved. In three cases of obsessive compulsive states, results were not satisfactory. In light of the factors of less disturbance to the total personality, absence of postoperative complications, shortened hospitalization, pecuniary savings and better clinical results, the authors prefer transorbital lobotomy to prefrontal lobotomy in private psychiatric practice and believe that in cases of frequent relapse early use of the procedure should be considered to prevent development of a chronic state.     

TRANSORBITAL LOBOTOMY—Its Use in Relapsing Psychotic States

Twenty-five private patients were treated by transorbital lobotomy. The period of observation after operation was from six months to three years. In 14 cases of affective disorders in which there was not adequate response to shock therapy, nine patients made social recovery and maintained good health and four were improved. Some follow-up shock therapy was necessary for about one-fifth of the patients. Of eight schizophrenic patients four made excellent social recoveries, two improved and two were not improved. In three cases of obsessive compulsive states, results were not satisfactory.In light of the factors of less disturbance to the total personality, absence of postoperative complications, shortened hospitalization, pecuniary savings and better clinical results, the authors prefer transorbital lobotomy to prefrontal lobotomy in private psychiatric practice and believe that in cases of frequent relapse early use of the procedure should be considered to prevent development of a chronic state.     

Changes in phospholipid composition of the mitochondrial membrane after orthotopic liver transplantation

Changes in phospholipids and their fatty acid composition in liver mitochondria obtained from allogenic rats with orthotopic liver transplants were measured with and without immunosuppressive treatment. In untreated allogenic rats, mitochondrial phosphorylation activity was severely deteriorated at 8 days after transplantation. A significant change was also found in the amount of cardiolipin compared with other classes of phospholipids. Namely, cardiolipin decreased, and lysodiphosphatidylglycerol and phosphatidylglycerol increased concomitantly. Furthermore, the percentage of linoleic acid in cardiolipin decreased dramatically. Decrease in cardiolipin and changes in its fatty acid composition may be attributed to the deterioration of mitochondrial function upon acute rejection.     

Right Anterior Insula: Core Region of Hallucinations in Cognitive Neurodegenerative Diseases

Objectives

We investigated the neural basis of hallucinations Alzheimer''s disease (AD) by applying voxel-based morphometry (VBM) to anatomical and functional data from the AD Neuroimaging Initiative.

Methods

AD patients with hallucinations, based on the Neuropsychiatric Inventory (NPI-Q) (AD-hallu group; n = 39), were compared to AD patients without hallucinations matched for age, sex, educational level, handedness and MMSE (AD-c group; n = 39). Focal brain volume on MRI was analyzed and compared between the two groups according to the VBM method. We also performed voxel-level correlations between brain volume and hallucinations intensity. A similar paradigm was used for the PET analysis. “Core regions” (i.e. regions identified in both MRI and PET analyses, simply done by retaining the clusters obtained from the two analyses that are overlapping) were then determined.

Results

Regions with relative atrophy in association with hallucinations were: anterior part of the right insula, left superior frontal gyrus and lingual gyri. Regions with relative hypometabolism in association with hallucinations were a large right ventral and dorsolateral prefrontal area. "Core region" in association with hallucinations was the right anterior part of the insula. Correlations between intensity of hallucinations and brain volume were found in the right anterior insula, precentral gyrus, superior temporal gyrus, and left precuneus. Correlations between intensity of hallucinations and brain hypometabolism were found in the left midcingulate gyrus. We checked the neuropathological status and we found that the 4 patients autopsied in the AD-hallu group had the mixed pathology AD and Dementia with Lewy bodies (DLB).

Conclusion

Neural basis of hallucinations in cognitive neurodegenerative diseases (AD or AD and DLB) include a right predominant anterior-posterior network, and the anterior insula as the core region. This study is coherent with the top-down/bottom-up hypotheses on hallucinations but also hypotheses of the key involvement of the anterior insula in hallucinations in cognitive neurodegenerative diseases.     

Effects of Acute and Chronic Attenuation of Postprandial Hyperglycemia on Postglucose-load Endothelial Function in Insulin Resistant Individuals: Is Stimulation of First Phase Insulin Secretion Beneficial for the Endothelial Function?

The aim of the study is to determine if attenuation of postprandial hyperglycemia, by acutely and chronically enhancing postprandial insulin secretion in insulin-resistant individuals, improves the endothelial dysfunction. We assessed postoral glucose-load endothelial function in 56 insulin-resistant subjects with the Flow-Mediated-Dilation (FMD) technique. We randomized subjects to intervention/control group, and examined the acute and chronic effect of nateglinide, an oral antidiabetic drug of rapid action. In the intervention group, postoral glucose-load (post-OGL) FMD delta values deteriorated when compared to pre-OGL values, most significantly at 3 h post-OGL, on the following days: on the first study day termed "Baseline day" (p=0.04); on both days after 3 months of nateglinide treatment [with nateglinide administered on study-day "acute+chronic" (p=0.01); and without nateglinide on study-day "Closing day", p=0.001]. Post-OGL changes in the control group were nonsignificant both at Baseline and on Closing day. After a single dose of nateglinide "Acute day", post-OGL FMD deterioration was abolished. There was an increment in post-OGL FMD delta values most significant at 2 h post-OGL (p=0.02). Insulin concentrations increased while glucose concentrations decreased on study-days with nateglinide when compared to study-days without (p=<0.001 for both insulin and glucose). Comparisons for insulin and glucose concentrations between days with nateglinide, and likewise between days without, showed no significant difference. Postglucose load endothelial dysfunction can be prevented by administration of nateglinide, however, after 3 months of nateglinide treatment, this effect is abolished. Chronically increased insulin secretion could counteract the initial beneficial effect of reduced glucose excursions. We found no relationship between postprandial hyperglycemia and post-OGL FMD.     

Rivastigmine as adjunctive therapy in the therapeutic dilemma for the treatment of hallucinations due to Parkinson disease

We report three cases of patients with Parkinson's disease without dementia, admitted to our hospital because of hallucinations. The anti-Parkinson medication was adapted and the patients started with rivastigmine. As a result, hallucinations no longer occurred. A 79 years old man also required short-term quetiapine because of agitation and anti-Parkinson doses were without side effects, as a result of which mobility improved. An 84 years old woman reported mild side effects of rivastigmine, without consequences, whereas her mobility appeared to be good. A 72 years old woman reported mild memory problems upon admission, which improved during admission, as did her mobility after increasing the anti-Parkinson medication doses. Treatment of rivastigmine can be useful in the therapeutic dilemma in the treatment of hallucinations in patients with Parkinson's disease (start anti-psychotic or reduce anti-Parkinson medication). In addition to adapting anti-Parkinson doses and sometimes short-term treating with an anti-psychotic, treatment with rivastigmine appears to be a quick improvement, without serious side effects. Also, mobility can improve, due to the possibility of increasing the anti-Parkinson doses, if necessary. Because of the many remaining questions, prospective randomised trials are needed.     

Bosentan in pulmonary arterial hypertension: a comparison between congenital heart disease and chronic pulmonary embolism

Background. In patients with pulmonary hypertension, it is unknown whether the treatment effect of bosentan is dependent on the duration of pulmonary vessel changes. Therefore, we studied the response to bosentan in patients with life-long pulmonary vessel changes (pulmonary arterial hypertension (PAH) due to congenital heart disease (CHD)) and in patients with subacutely induced pulmonary vessel changes (chronic thromboembolic pulmonary hypertension (CTEPH)). Methods. In this open-label study, 18 patients with PAH due to CHD and 16 patients with CTEPH were treated with bosentan for at least one year. All patients were evaluated at baseline and during follow-up by means of the six-minute walk distance (6-MWD) and laboratory tests. Results. Improvement of 6-MWD was comparable in patients with PAH due to CHD (444±112 m to 471±100 m, p=0.02), and in CTEPH (376±152 m to 423±141 m, p=0.03) after three months of treatment. After this improvement, 6-MWD stabilised in both groups. Conclusion. Although duration of pulmonary vessel changes is strikingly different in patients with PAH due to CHD and CTEPH, the effect of one year of bosentan treatment was comparable. The main treatment effect appears to be disease stabilisation and decreasing the rate of deterioration. (Neth Heart J 2009;17:334–8.)     

Rivastigmine als ondersteuning bij het dilemma van de behandeling van hallucinaties optredend bij ziekte van Parkinson

We report three cases of patients with Parkinson’s disease without dementia, admitted to our hospital because of hallucinations. The anti-Parkinson medication was adapted and the patients started with rivastigmine. As a result, hallucinations no longer occurred. A 79 years old man also required short-term quetiapine because of agitation and anti-Parkinson doses were without side effects, as a result of which mobility improved. An 84 years old woman reported mild side effects of rivastigmine, without consequences, whereas her mobility appeared to be good. A 72 years old woman reported mild memory problems upon admission, which improved during admission, as did her mobility after increasing the anti-Parkinson medication doses. Treatment of rivastigmine can be useful in the therapeutic dilemma in the treatment of hallucinations in patients with Parkinson’s disease (start anti-psychotic or reduce anti-Parkinson medication). In addition to adapting anti-Parkinson doses and sometimes short-term treating with an anti-psychotic, treatment with rivastigmine appears to be a quick improvement, without serious side effects. Also, mobility can improve, due to the possibility of increasing the anti-Parkinson doses, if necessary. Because of the many remaining questions, prospective randomised trials are needed.     

Treatment of adolescents with depression: the effect of transference interventions in a randomized controlled study of dynamic psychotherapy

ABSTRACT: BACKGROUND: Depression in adolescents seems to be a growing problem that causes mental suffering and prevents young people from joining the workforce. There is also a high risk of relapse during adult life. There is emerging evidence for the effect of psychodynamic psychotherapy in adolescents. In-session relational intervention (that is, transference intervention) is a key component of psychodynamic psychotherapy. However, whether depressed adolescents profit most from psychodynamic psychotherapy with or without transference interventions has not been stated. Object The effect of transference interventions in depressed adolescents and the moderator moderating effect of quality of object relations, personality disorder and gender will be explored. Methods and study design The First Experimental Study of Transference Work--In Teenagers (FEST--IT) will be a randomized clinical trial with a dismantling design. The study is aimed to explore the effects of transference work in psychodynamic psychotherapy for adolescents with depression. One hundred patients ages 16 to 18 years old will be randomized to one of two treatment groups, in both of which general psychodynamic techniques will be used. The patients will be treated over 28 weeks with either a moderate level of transference intervention or no transference intervention. Follow-up will be at 1 year after treatment termination. The outcome measures will be the Psychodynamic Functioning Scales (PFS), Inventory of Interpersonal Problems--Circumplex Version (IIP-C), Global Assessment of Functioning (GAF), and the total mean score of Symptom Checklist--90 (Global Severity Index; GSI), Beck Depression Inventory (BDI), and Montgomery Asberg Rating Scale (MADRS). The quality of adolescents' relationships will be a central focus of the study, and the Adolescent Relationship Scales (ARS) and Differentiation--Relatedness Scale (DRS) will also be used. Change will be assessed using linear-mixed models. Gender personality disorder (PD) and quality of object relations (QOR) will be the preselected putative moderators. DISCUSSION: The object of this clinical trial is to explore the effect of transference interventions in psychodynamic psychotherapy in adolescents with a major depressive disorder. Using a randomized and dismantling design, we hope that the study will add more specific knowledge to the evidence base. Trial registration ClinicalTrials.gov Identifier: NCT01531101 First Experimental Study of Transference work Work--In Teenagers (FEST-IT).     

Subclinical Elevation of Plasma C-Reactive Protein and Illusions/Hallucinations in Subjects with Parkinson’s Disease: Case–control Study

Background

Though infections are associated with psychotic symptoms, whether or not subclinical inflammation is associated with hallucinations is not known in Parkinson’s disease (PD).

Purpose

To investigate the association of illusions/hallucinations and plasma CRP levels in PD patients without symptomatic infections.

Methods

PD patients not diagnosed as having infections were assessed for illusions and hallucinations using the Parkinson Psychosis Questionnaire (PPQ). It comprises four-domain questions: PPQ-A for sleep problems, PPQ-B for hallucinations/illusions, PPQ-C for delusions, and PPQ-D for disorientation. Assigning patients with ≥1 points in the PPQ-B score to be cases and others as controls, the association of hallucinations/illusions and clinical features (age, sex, duration of PD, Unified Parkinson’s Disease Rating Scale part 3 (UPDRS-3), Mini-Mental State Examination (MMSE) score, sleep disturbance (PPQ-A score) as well as daily doses of L-Dopa, dopamine agonists, amantadine, and selegiline) were analyzed using a case–control design.

Results

A total of 111 patients were examined and plasma CRP levels were <0.1–6.0 mg/L. Hallucinations or illusions were detected in 28 (25.2%). There were significant differences in age, UPDRS-3 score, MMSE score, PPQ-A, daily doses of L-Dopa and dopamine agonists and plasma CRP levels between cases and controls. A multivariate logistic regression model revealed that UPDRS-3 scores and plasma CRP levels were significantly associated with hallucinations/illusions with an adjusted odds ratio of 1.96 (95% confidence interval (CI) 1.20–3.20) per 10 points and 1.57 (95% confidence interval 1.13–2.16) per two-fold, respectively. Dividing patients into thirds by CRP levels (≤0.2, 0.3–0.6, ≥0.7 mg/L), the prevalence of hallucinations/illusions was 13.2%, 21.6%, and 41.7%, in the bottom-, middle-, and top-thirds, respectively (for trend p = 0.012).

Conclusions

Subclinical elevation of plasma CRP levels was associated with hallucinations or illusions after adjustment for motor disability, suggesting that subclinical elevations of CRP levels might be an independent risk for hallucinations/illusions.     

Short and Long Term Effects of Left and Bilateral Repetitive Transcranial Magnetic Stimulation in Schizophrenia Patients with Auditory Verbal Hallucinations: A Randomized Controlled Trial

Background

Repetitive transcranial magnetic stimulation of the left temporo-parietal junction area has been studied as a treatment option for auditory verbal hallucinations. Although the right temporo-parietal junction area has also shown involvement in the genesis of auditory verbal hallucinations, no studies have used bilateral stimulation. Moreover, little is known about durability effects. We studied the short and long term effects of 1 Hz treatment of the left temporo-parietal junction area in schizophrenia patients with persistent auditory verbal hallucinations, compared to sham stimulation, and added an extra treatment arm of bilateral TPJ area stimulation.

Methods

In this randomized controlled trial, 51 patients diagnosed with schizophrenia and persistent auditory verbal hallucinations were randomly allocated to treatment of the left or bilateral temporo-parietal junction area or sham treatment. Patients were treated for six days, twice daily for 20 minutes. Short term efficacy was measured with the Positive and Negative Syndrome Scale (PANSS), the Auditory Hallucinations Rating Scale (AHRS), and the Positive and Negative Affect Scale (PANAS). We included follow-up measures with the AHRS and PANAS at four weeks and three months.

Results

The interaction between time and treatment for Hallucination item P3 of the PANSS showed a trend for significance, caused by a small reduction of scores in the left group. Although self-reported hallucination scores, as measured with the AHRS and PANAS, decreased significantly during the trial period, there were no differences between the three treatment groups.

Conclusion

We did not find convincing evidence for the efficacy of left-sided rTMS, compared to sham rTMS. Moreover, bilateral rTMS was not superior over left rTMS or sham in improving AVH. Optimizing treatment parameters may result in stronger evidence for the efficacy of rTMS treatment of AVH. Moreover, future research should consider investigating factors predicting individual response.

Trial Registration

Dutch Trial Register NTR1813     

Solvent encephalopathy.

Nineteen children aged 8-14 years were admitted over a six-year period with an acute encephalopathy due to toluene intoxication. Seven had a history of euphoria and hallucinations. The remainder presented with coma (4), ataxia (3), convulsions (3), and behaviour disturbance with diplopia (2), A history of glue sniffing was elicited in 14, but in the remainder toluene assay confirmed the diagnosis. Thirteen children recovered completely; five still had psychological impairment and personality change on discharge from hospital but were lost to follow-up, and one has a persistent cerebellar ataxia one year after the acute episode, despite absence of further exposure. Toluene inhalation is an important cause of encephalopathy in children and may lead to permanent neurological damage. Diagnosis is most important if further damage due to continued abuse is to be prevented, and toluene assay is a valuable aid to diagnosis.     

Cholesterol biosynthesis from birth to adulthood in a mouse model for 7-dehydrosterol reductase deficiency (Smith-Lemli-Opitz syndrome)

Smith-Lemli-Opitz syndrome (SLOS) is caused by deficiency in the terminal step of cholesterol biosynthesis, which is catalyzed by 7-dehydrocholesterol reductase (DHCR7). The disorder exhibits several phenotypic traits including dysmorphia and mental retardation with a broad range of severity. Pathogenesis of SLOS is complex due to multiple roles of cholesterol and may be further complicated by unknown effects of aberrant metabolites that arise when 7-dehydrocholesterol (7-DHC), the substrate for DHCR7, accumulates. A viable mouse model for SLOS has recently been developed, and here we characterize cholesterol metabolism in this model with emphasis on changes during the first few weeks of postnatal development. Cholesterol and 7-DHC were measured in "SLOS" mice and compared with measurements in normal mice. SLOS mice had measurable levels of 7-DHC at all ages tested (up to 1 year), while 7-DHC was below the threshold for detection in normal mice. In perinatal to weaning age SLOS mice, cholesterol and 7-DHC levels changed dramatically. Changes in brain and liver were independent; in brain cholesterol increased several fold while 7-DHC remained relatively constant, but in liver cholesterol first increased then decreased again while 7-DHC first decreased then increased. In older SLOS animals the ratio of 7-DHC/cholesterol, which is an index of biochemical severity, tended to approach, but not reach, normal. While these mice provide the best available genetic animal model for the study of SLOS pathogenesis and treatment, they probably will be most useful at early ages when the metabolic effects of the mutations are most dramatic. To correlate any experimental treatment with improved sterol metabolism will require age-matched controls. Finally, determining the mechanism by which these "SLOS" mice tend to normalize may provide insight into the future development of therapy.     

Rapid tightening of blood glucose control leads to transient deterioration of retinopathy in insulin dependent diabetes mellitus: the Oslo study.

In a study of retinopathy during one year of tight blood glucose control 45 type I (insulin dependent) diabetics without proliferative retinopathy were randomised to receive either continuous subcutaneous insulin infusion, multiple insulin injections, or conventional insulin treatment (controls). Near normoglycaemia was achieved with continuous infusion and multiple injections but not with conventional treatment. Blind evaluation of fluorescein angiograms performed three monthly showed progression of retinopathy in the control group, transient deterioration in the continuous infusion group, and no change in the multiple injection group. Half the patients receiving continuous infusion and multiple injections developed retinal cotton wool spots after three to six months. These changes regressed in all but four patients after 12 months. Control patients did not develop cotton wool spots. Patients who developed cotton wool spots are characterised by a larger decrement in glycosylated haemoglobin and blood glucose values, more frequent episodes of hypoglycaemia, a longer duration of diabetes, and more severe retinopathy at onset. A large and rapid fall in blood glucose concentration may promote transient deterioration of diabetic retinopathy.     

Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy.

The effects of angiotensin converting enzyme inhibition with captopril were investigated in patients with diabetic nephropathy and hypertension. After nine days'' treatment with captopril glomerular filtration rate was unchanged in 13 patients, whereas renal plasma flow had increased from 265 to 302 ml/min/1.73 m2 body surface area (p less than 0.05) and the filtration fraction had decreased from 14.3 to 12.8% (p less than 0.025). During two years'' treatment with captopril in 14 patients the mean arterial blood pressure had fallen by 5 mm Hg (p less than 0.005) and the deterioration in glomerular filtration rate had decreased from 10.3 to 2.4 ml/min/year (p less than 0.005). There was no correlation between the fall in blood pressure and the reduction in the deterioration of glomerular filtration rate. These findings suggest that the effects of angiotensin converting enzyme inhibition on renal haemodynamics protect renal function. Inhibitors of angiotensin converting enzyme should be considered for lowering blood pressure in patients with diabetic nephropathy.     

Influence of personality disorder on the treatment of panic disorder--comparison study

Most clinicians tend to believe that the occurrence of the anxiety disorder in comorbidity with a personality disorder often leads to longer treatment, worsens the prognosis, and thus increasing treatment costs. The study is designed to compare the short-term effectiveness of combination of cognitive behavioral therapy and pharmacotherapy in patient suffering with panic disorder with and without personality disorder. METHOD: We compare the efficacy of 6th week therapeutic program and 6th week follow up in patients suffering with panic disorder and/or agoraphobia and comorbid personality disorder (29 patients) and panic disorder and/or agoraphobia without comorbid personality disorder (31 patients). Diagnosis was done according to the ICD-10 research diagnostic criteria confirmed with MINI and support with psychological methods: IPDE, MCMI-III and TCI. Patients were treated with CBT and psychopharmacs. They were regularly assessed in week 0, 2, 4, 6 and 12 by an independent reviewer on the CGI (Clinical Global Improvement) for severity and change, PDSS (Panic Disorder Severity Scale), HAMA (Hamilton Anxiety Rating Scale), SDS (Sheehan Disability Scale), HDRS (Hamilton Depression Rating Scale), and in self-assessments BAI (Beck Anxiety Inventory) and BDI (Beck Depression Inventory). RESULTS: A combination of CBT and pharmacotherapy proved to be the effective treatment of patients suffering with panic disorder and/or agoraphobia with or without comorbid personality disorder. The 12th week treatment efficacy in the patients with panic disorder without personality disorder had been showed significantly better compared with the group with panic disorder comorbid with personality disorder in CGI and specific inventory for panic disorder--PDSS. Also the scores in depression inventories HDRS and BDI showed significantly higher decrease during the treatment comparing with group without personality disorder. But the treatment effect between groups did not differ in objective anxiety scale HAMA, and subjective anxiety scale BAI.