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Depression ist heutzutage weltweit eine der h��ufigsten psychischen Erkrankungen. Daher gewinnt die Therapie dieser Erkrankung mehr an Bedeutung. Die Auswahl der Antidepressiva basiert zurzeit nur auf unspezifischen Kriterien. Eine personalisierte Therapie mit Biomarkern wird daher immer mehr angestrebt. Biomarker sollten in klinischen Studien reproduzierbar sein. Ziel dieser Studie ist es ein m��gliches reproduzierbares Modell zu untersuchen um zuk��nftige Biomarker zu identifizieren. Dazu wurden 33 Lymphoblastoide Zelllinien (LCL) von Patienten, deren klinischer Verlauf bekannt ist, aus der Munich Antidepressant Response Signature-Studie (MARS) gewonnen, der wachstumshemmende Effekt von Imipramin, Paroxetin, Mirtazapin und Epigallocatechingallat (EGCG) sowie die Konzentration und Genexpression von potentiellen Biomarkern (Brain-derived neurotrophic factor (BDNF), dessen Vorl��ufer ProBDNF und Cell adhesion molecule with homology to L1CAM (CHL1)) untersucht und von den Probanden der BDNF Genotyp bez��glich Val66Met-Polymorphismus erhoben. LCLs sind mit Ebstein-Barr-Virus immortalisierte B-Lymphozyten, die die genetischen und epigenetischen Eigenschaften der Testpersonen wiederspiegeln. Ein Ergebnis unserer Studie zeigte, dass LCLs ein individuelles und klassenspezifisches Verhalten auf die wachstumshemmenden Effekte der Antidepressiva und EGCG haben. Des Weiteren wurde eine Korrelation zwischen klinischen Daten, z.B. f��nf Wochen Response und acht Wochen Remission und den erhobenen Daten untersucht. Imipramin zeigte bei niedriger Konzentration eine Zellproliferation. Diese Ergebnisse korrelieren mit der f��nf Wochen-Response (p = 0,035). Mit diesen Versuchen und den klinischen Daten konnte gezeigt werden, dass Lymphoblastoide Zelllinien ein m��gliches Modell zur Biomarkerfindung darstellen. Es m��ssen jedoch noch weitere Untersuchungen durchgef��hrt werden.

Rhodiola rosea (Eisenwurz) ist eine Hochgebirgspflanze aus den arktischen Gebieten Europas und Asiens, die als einzige aller Rhodiola-Arten spezifische Wirkstoffe, namlich die Phenylpropanoide, beinhaltet. Rhodiola rosea wirkt beruhigend, antidepressiv, antriebssteigernd und stressmodulierend und moduliert Dopamin und Serotonin im Gehirn; Extrakte aus dem Rhizom konnen in Kombination mit anderen Arzneimitteln Nebenwirkungen mit sich bringen. Anhand eines Fallberichts soll dieser Zusammenhang beschrieben werden. Wir berichten uber eine 68-jahrige Patientin mit rezidivierender mittelgradiger Depression mit somatischem Syndrom (ICD-10 F33.11), die unter der Selbstmedikation von Eisenwurz bei gleichzeitiger Einnahme von Paroxetin u. a. vegetative Syndrome, Unruhe-Gefuhl und leichtes Zittern entwickelt hatte. Rhodiola rosea kann mit anderen Arzneimitteln pharmakokinetische sowie -dynamische Interaktionsphanomene auslosen. Das Auftreten der Symptome der Patientin lasst sich am ehesten als serotonerges Syndrom erklaren. Aufgrund der weitverbreiteten Verschreibung der Pflanze sollte an Wechselwirkungen und Risikoprofile gedacht werden.

Anxiety disorders today are regarded as very treatable conditions, provided that pharmaco- and/or psychotherapy are implemented according to evidence-based guidelines. The family physician treats primarily with pharmaceutical preparations. For this, a series of antidepressants, mainly belonging to the SSRI and SNRI substance groups, are available. Among the psychotherapeutic methods, cognitive behavior and confrontation therapies have been proven successful.

The serotonin-syndrome is a possible side-effect in the treatment with serotonergic drugs. There are diagnostic criteria for diagnosis of this syndrome. After discontinuation of administering the serotonergic drug is fully reversible.

So far, there have only been few studies concerning the question of indication and efficacy of antidepressive medication in children and adolescents with anorexia nervosa and depressive episode in the course of an inpatient treatment. In addition, there is a lack of studies comparing the tolerability and efficacy of different antidepressants given to anorectic patients of this particular age group. This study compares paroxetine, a specific SRI, with clomipramine, a TCA with SRI activity, concerning the frequency and quality of adverse side effects, the frequency and the reasons for discontinuating the antidepressive treatment and different outcome measurements.83 female patients, aged 10.9 to 18.1 years, who underwent an inpatient treatment at the Departement of Child and Adolescent Psychiatry and Psychotherapy at the University of Wuerzburg, Germany, were enrolled in this retrospective study. All of them met the ICD-10 criteria for anorexia nervosa and depressive episode and received an antidepressant medication with clomipramine or paroxetine. We collected data from basic documentation, treatment reports, and the multiaxial classification (MAS). Outcome measurements were the duration of treatment (days) and the increase of body weight (kg/m2).The discontinuation of the antidepressive treatment due to adverse side effects or a lack of efficacy was significantly more frequent with clomipramine than paroxetine (33.3 vs. 15.4%). The increase of body weight (2.8 vs. 2.6 kg/m2) was similar in both groups, but the duration of treatment was significantly shorter under paroxetine (71.9 vs. 96.5 days).A shorter duration of treatment, faster increase of body weight, lower percentage of dicontinuating the antidepressive medication and last but not least economic reasons lead to the conclusion, that paroxetine should be preferred in female adolescents with anorexia nervosa and depressive episode. However, prospective studies are needed to confirm our findings.

Paroxetine, a selective serotonin reuptake inhibitor (SSRI) may be given in severe cases of maternal depression and panic disorders during pregnancy. However, it may lead to severe withdrawal symptoms: respiratory distress, jitteriness, convulsions, hypoglycaemia, an impaired muscle tone and necrotising enterocolitis. These symptoms, also called neonatal withdrawal syndrome, may last up to one month. We report a girl born at 37 weeks of gestation presenting 12 hours after birth with hypopnea, bradycardia and a decreased muscular tone of unknown origin. The child was transferred to the NICU and was intubated and ventilated mechanically. Within the first days the patient also developed cerebral seizures. The EEG showed severe abnormalities. Later we learned that the patient's mother had been treated with Paroxetine during pregnancy. The patient recovered after two days of ventilation and anticonvulsive medication with phenobarbital. The EEG result showed a siginificant improvement. At day 10 she was discharged in good condition. Recognition and treatment of the presented neonatal problems could have been more effective and faster, if the attending pediatricians had been informed earlier about the maternal medication with SSRIs. Neonates of mothers who were treated with SSRIs during pregnancy should be monitored. Paroxetine withdrawal syndrome should be considered as one of the differential diagnosis of neonatal encephalopathy.

Obsessive-compulsive disorder (OCD) is characterized by obsessions, compulsions, or both, which cause significant personal distress or social dysfunction. OCD is a common psychiatric illness with a prevalence of 1-2%. Because most people have regular contact with primary health care services, the patient with OCD is likely to see their general practitioner even though psychological problems may not be the main reason for consultation. Early recognition of the disorder facilitates early intervention. This reduces distress, disability and burden of illness. Pharmacological treatment with serotonin reuptake inhibitors (SRI) and cognitive-behavioral therapy have both been proven to be effective and are evidence based.

A new depressive entity called the "Sisi syndrome," named in reference to the former empress of Austria, was introduced by a drug company in 1998. Their advertising campaign presents information about nosology, symptoms, and recommended therapy. We review the relevant literature about this syndrome and are not able to confirm the statements about it. The lack of scientific proof of it as an independent entity of depression stands in contrast to the widespread media coverage in Germany, which was organized by a public relations company. Therefore, we discuss new kinds of marketing strategies ("disease mongering") by drug companies and conclude with some preventive recommendations.

This paper presents a valid animal model of innate anxiety/depression: anxious (HAB) or non-anxious (LAB) rats, which show stable and robust responses in a variety of ethological tests. In addition to their extreme anxiety-related behavior, HAB animals are characterized by passive stress coping, an activated stress (HPA) axis, and increased stress vulnerability. The enhanced expression and release of arginine vasopressin (AVP) in the hypothalamus of HAB rats seem to underlie these phenomena. Accordingly, an AVP receptor antagonist attenuates anxiety-related behavior and normalizes the HPA axis and the dexamethasone/CRH test. Treatment with the antidepressive drug paroxetine reduces the overexpression of AVP and normalizes both the depression-like behavior and neuroendocrine correlates of anxiety/depression. The complex phenotyping led us to the conclusion that the AVP gene is likely to be a candidate gene of inborn anxiety. Partial genotyping of HAB animals results in the identification of polymorphisms (SNPs) in the promoter domain of the AVP gene, thus potentially leading to novel strategies of diagnosis and therapy of anxiety disorders and depression.

This case report deals with the day care treatment of two seven- and eight-year-old siblings with elective mutism. Their treatment entails a combination of psychopharmacological and intensive behavior therapy. The multimodal therapeutic process is presented together with continuing psychosocial steps. Behavioral intervention focuses on building verbal expressive capacity, reducing speech anxiety in social situations and generalization to non-therapeutic situations. The case report is discussed in the context of the current literature on elective mutism.

Tardive dyskinesia is a severe complication of neuroleptic treatment. It may develop weeks, even years after starting a neuroleptic treatment and the symptoms may be irreversible. Neuroleptic compounds are not only used in cases of schizophrenia, but also in cases of severe depression with delusional symptoms. We want to present the case of a 67 year old female patient who developed haloperidol induced dyskinesea and stress unto the successful treatment of this complication with olanzapine in combination with paroxetine. Under this regime not only the improvement of the depression, but also of the tardive dyskinesea was impressive.

A 57-year-old woman, a heavy smoker and migraine sufferer, was admitted with severe resting pain in the right forefoot and painful localized tendril-shaped reddening on the right thigh. She had regularly been taking 1-2 mg ergotamine tartrate, several analgesics, some containing caffeine, and selective serotonin-uptake inhibitors. Clinical examination found all limbs to be cool. On the right leg the pulse was not palpable below the inguinal line, and the reddening corresponded to localized livedo.The peripheral Doppler pressure indicated critical perfusion reduction in the right leg with a tibiobrachial pressure ratio of 0.14. Colour-coded duplex sonography showed generalized vasoconstriction with filiform hourglass stenosis of the right proximal superficial femoral artery without atherosclerotic changes. The history of drug intake and the characteristic sonographic findings indicated ergotism and an arteriography was deemed unnecessary.All ergotamine and caffeine containing drugs were discontinued and the patient urged to stop smoking. Amlidopine, 2.5 mg orally, and prostaglandin E1, 60 microgram i.v., were administered daily. The resting pain was much reduced after the first infusion and the painful livedo disappeared. The documented high-grade stenosis of the right superficial femoral artery was reduced to 25-50% by the third day of infusion. At the end of 10 daily infusions both the Doppler pressure and the duplex sonography had become normal. Pizotifen was given for the migraine and the serotonin re-uptake inhibitor sertralin was discontinued.An interaction of the serotonin re-uptake inhibitor with ergotamine was presumably responsible for the development of ergotism undertherapeuticergotamine dosage. Vasospastic stenoses and occlusions can be demonstrated by duplex sonography and may in future not require additional angiographic confirmation. Intravenous rather than intraarterial infusion of prostaglandin is to be preferred if vessels at many sites are affected. Livedo is a transitory sign of ergotism.

In a 71 years-old patient, a severe therapy-resistant depressive episode without psychotic symptoms was successfully treated by a combination of paroxetine and risperidone. Previously, several different antidepressants were not effective in ameliorating the depressive symptoms which occurred repeatedly over a period of more than ten years.

We report on a 62 year old female patient treated with paroxetine, a selective serotonin reuptake inhibitor, because of an anxiety neurosis undergoing a vaginal hysterectomy in general anesthesia. Apart from a dietary treated diabetes mellitus there were no other diseases. There were no complications during the operation. At the end of the anesthesia an A-V nodal tachycardia appeared which spontaneously changed to a sinus rhythm ten hours after the end of the operation. No clinical or laboratory findings indicated a cardiac ischemia and an additional Holter ECG-Recording showed no further cardiac arrhythmias. No other complications occurred afterwards and the patient was discharged after two weeks. This case report demonstrates clearly that despite a reduced rate of cardiovascular complications compared to other types of antidepressants selective serotonin reuptake inhibitors can lead to perioperative cardiac arrhythmias.

Depression is a common problem in neurological rehabilitation. Although three double-blind studies have shown the efficacy of trazodone, citalopram and nortriptyline, antidepressant drug therapy of poststroke depression is not yet considered a state-of-the-art strategy. In a hospital for neurological rehabilitation we have performed an open study on the effects of the SSRI, paroxetine, in depressive disorders caused by neurological diseases.111 consecutive admissions were screened for depression and 9 patients were admitted to the study having a HDRS scoreor = 14.10-40 mg of paroxetine were well tolerated and led to aor = 50% reduction of the HDRS score in 8/9 patients. A patient with pathological crying, but without depression, was also successfully treated with 20 mg of paroxetine.We conclude that the SSRI, paroxetine, is an effective and well-tolerated therapy of depressive disorders caused by various neurological diseases, including also other diagnoses than stroke.

One possible side effect of selective serotonin re-uptake inhibitors (SSRI) is the exacerbation of nervous tics in a 12-year-old boy treated with tiapride following prescription of paroxetine for a depressive syndrome. Potential causal factors include residual cholinergic activity of paroxetine, the observably increased drive under paroxetine, metabolic properties, and protein binding. The problem of side effects under selective serotonin re-uptake inhibitors, as well as the issues of co-morbidity and co-medication in the treatment of nervous tics and Tourette's Syndrome are discussed.

In this double-blind, non-placebo controlled study [corrected], 179 patients with treated breast cancer who fulfilled the ICD-10 criteria for an acute depressive episode underwent an 8-week course of antidepressant treatment with either the tricyclic amitriptyline (75-150 mg, n = 87) or the serotonin-reuptake inhibitor paroxetine (20-40 mg, n = 88).The change in clinical status relative to baseline was measured with the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression (CGI), the Functional Living Index-Cancer (FLIC) and the Patient Global Evaluation.Both treatment groups showed significant improvement in all parameters at weeks 3, 5 and 8. At no time was there a significant difference in the efficacy of the antidepressants used. Adverse events, most of which were transitory, were reported by 53% of the patients in the paroxetine group and 60% in the amitriptyline group. The 8-week treatment was completed by 81% of the paroxetine and 76% of the amitriptyline patients.The results of this study show that depression in breast-cancer patients can be correctly diagnosed and adequately treated by non-psychiatrists. The treatment with both medications was carried out in dose ranges which correspond to that employed in physically well patients.

A young nurse was found dead in her flat. In chemical-toxicological analysis the following femoral blood drug concentrations were determined: paroxetine 0.176 mg/l, doxepine 82.12 mg/l, desmethyldoxepine 0.34 mg/l. Additionally the drug concentrations were determined in various body fluids and organs. The results of the described fatality are discussed. For interpretation of toxicologic results in antidepressant fatalities ratios of parent drug to metabolite and postmortem drug redistribution should be taken into account.

Selective serotonin reuptake inhibitors (SSRI) are known to exhibit far less cardiac side effects than tricyclic antidepressants. We report three cases in which the SSRI, paroxetine, induced clinically relevant ECG changes in patients with high risk profile. In two cases an increase in QTc time was observed, severe bradycardia was also observed twice.

We report on a 22-year-old schizophrenic patient who attempted suicide and suffered an epidural hemorrhage. 16 days after the neurosurgical operation. After several weeks of treatment with promethazine, 1 day after intake of paroxetin he partially lost consciousness and developed extrapyramidal symptoms and vegetative disorders. Hyper-Ck-aemia up to 680 U/l was observed. Malignant neuroleptic syndrome (MNS) was diagnosed, which led to withdrawal of paroxetin and promethazine. He was put on dantamacrine and amantadine until the symptoms resolved. To date there have been few reports on MNS under tricyclic antidepressants and selective serotonin inhibitors. The influence of the central serotonergic system on the pathophysiology of MNS is discussed.

Because of their low incidence of adverse effects SSRI are prescribed more and more frequently in patients with depressive disorders. SSRI inhibit different subsystems of cytochrome-P 450-oxydase. Especially during co-administration of SSRI with antipsychotic and antiarrhythmic drugs pharmacokinetic interactions have to be observed carefully. In this presentation a case of bradycardia after co-administration of paroxetine and metoprolol is reported. Drug history and a careful drug monitoring are necessary requirements to avoid serious adverse effects.

Depressive stupor and malignant neuroleptic syndrome are very well-known problems in clinical psychiatry. The serotonin syndrome, however, a potentially life-threatening side effect of treatment with serotonergic substances, has been included in the clinical differential diagnosis increasingly often in the last few years. The development of new serotonin selective antidepressants and selective reversible inhibitors of monoamine oxidase A has led to the use of more and more substances that can cause these life-threatening complications if they are taken in too high doses or together with other drugs. We present a 61 year old depressed female impatient who developed an abortive malignant neuroleptic syndrome while being treated for depressive stupor. We discuss a possible relation between serotonin syndrome and a highly dosed combination therapy with moclobemide. Owing to the importance of both syndromes, we consider drug monitoring absolutely necessary for patients who are being treated with new antidepressants, and especially for those who develop neurological and psychiatric complications when such preparations are given in combination with other drugs.

A 6-week double-blind, parallel group study compared paroxetine and fluoxetine in 106 depressed geriatric inpatients (aged 65 to 85 years). Patients presenting acutely with major depressive episode DSM-III-R 296.2 (HAMD18 on 21 item scale) were randomized to receive paroxetine (20-40 mg, n = 54) or fluoxetine (20-60 mg, n = 52) following a 3-7 day washout. Primary criteria was the reduction of Hamilton Depression Rating Scale Score (HAMD). Furthermore Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression Scale (CGI) were used. Cognitive functions were assessed with the Mini-Mental-State Examination (MMSE) and the Sandoz Clinical Assessment Geriatric Scale (SCAG). The results showed a comparable reduction in the depression rating scales between the two treatment groups after 6 weeks. However, there was a statistically significant difference (p0.05) in HAMD, MADRS, SCAG, MMSE and cognitive subscales of HAMD and SCAG at week 3 in favour of paroxetine, which even was seen after 6 weeks in the SCAG. There were no significant differences between the treatment groups and the number of adverse events reported or in overall tolerability.

The influence of paroxetine (1x20 mg/day) on safety-relevant performance was compared with the effects of doxepin (2x50 mg/day) and placebo. The medication covered a 3-week period. On day 20 of treatment, ethanol was additionally administered (0.05% BAC). The study group comprised 60 healthy male and female volunteers in the age range 37-60 years, who were assigned to the three structurally identical medication groups under randomized, double-blind conditions. The functional capacity of primary interest was investigated in seven tests to record visual orientation, forced concentration, simple reaction time, choice reaction time, reaction under stress, vigilance, and motor co-ordination. Test sessions took place before the treatment and five times during the medication phase. Paroxetine proved comparable to placebo in all cases, while in comparison with the two reference substances doxepin revealed loss of vigilance and motor coordination, as well as of concentration and the simple (acoustic) reaction time.

The SSRIs are a new class of effective antidepressant agents which have proven efficacy in a wide range of psychiatric applications. They are as effective as the tricyclic antidepressants and are better tolerated. The SSRIs are safe in overdose and have minimal drug interactions, and are suitable for once-daily dosing. Newer members of the class, such as paroxetine, have shorter half-lives and no active metabolites, and are likely to be safer than other members of the class. Paroxetine has been compared with the standard tricyclic antidepressants in a range of studies, and the efficacy and tolerability data from these studies have been collected together in the worldwide database on paroxetine. Paroxetine was shown to be at least as effective as active comparators in melancholic depression (DSM-III). In a comparative study of paroxetine and fluoxetine, both drugs were effective in reducing depressive symptoms and paroxetine showed a faster onset of action than fluoxetine. A higher incidence of side-effects was obtained in fluoxetine patients. In a long-term comparative study of paroxetine and placebo, fewer patients relapsed while on paroxetine for one year than on placebo--15 and 38%, respectively.

We report the case history of two female schizophrenic in-patients who exhibited a significant reduction of accompanying obsessive-compulsive symptoms under the combined treatment of neuroleptics and selective serotonin reuptake inhibitors (SSRIs). Our results indicate that the basic psychotic disorder was not exacerbated as a result of this additional treatment.