The Therapeutic Potential of Non Steroidal Anti-inflammatory Drugs in the Treatment of Depression and Schizophrenia

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
N. Müller ◽  
M. Riedel ◽  
M.J. Schwarz
Keyword(s):  
Therapeutic Effect ◽  
Proinflammatory Cytokines ◽  
Therapeutic Potential ◽  
Disease Process ◽  
Antidepressant Effect ◽  
Double Blind Study ◽  
Double Blind ◽  
Cardiovascular Side Effects ◽  
Cox 2 ◽  
Cox 2 Inhibitors

COX-2 inhibition seems to balance the type-1/type-2 immune response, possibly via inhibition of prostaglandin E2. COX-2 inhibition reduces proinflammatory cytokines. COX-2 inhibition has an impact to the glutamatergic neurotransmission and influences the tryptophan/kynurenine metabolism: all three components seem to be involved in the pathophysiology of psychiatric disorders, particularly in schizophrenia and major depression.Due to the increase of proinflammatory cytokines and PGE2 in depressed patients, antiinflammatory treatment would be expected to show antidepressant effects. An antidepressant effect of rofecoxib was found in patients with osteoarthritis. An own randomized double blind pilot add-on study using the selective COX-2 inhibitor celecoxib in MD showed a significant therapeutic effect of the COX-2 inhibitor on depressive symptoms. Although those preliminary data have to be interpreted cautiously, those results are encouraging for further studies dealing with the inflammatory hypothesis of depression.Secondly, we and other research-groups performed several studies of COX-2 inhibitors in schizophrenia. In a prospective, randomized, double-blind study with the COX-2 inhibitor celecoxib in acute exacerbation of schizophrenia, a therapeutic effect of celecoxib was observed. The finding of a clinical advantage of COX-2 inhibition could not be replicated in a second study. Further analysis of the data revealed that the efficacy of therapy with a COX-2 inhibitor seems most pronounced in the first years of the schizophrenic disease process.It has to be considered, however, that therapy with COX-2 inhibitors is currently under discussion - as therapy with other non-steroidal antiphlogistics - due to cardiovascular side-effects.

Anti-inflammatory treatment approaches in major depression

2011 ◽  
Vol 26 (S2) ◽  
pp. 2093-2093 ◽  
Author(s):  
N. Müller ◽  
M.J. Schwarz
Keyword(s):  
Major Depression ◽  
Proinflammatory Cytokines ◽  
Psychiatric Patients ◽  
Double Blind Study ◽  
Double Blind ◽  
Depressed Patients ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Significant Therapeutic Effect

Proinflammatory cytokines, such as IL-6, IL-1 and TNF-a appear to be elevated at least in the peripheral blood of depressed patients. Thus, the activity of the enzyme IDO, which is driven by pro-inflammatory cytokines and regulates the tryptophan/kynurenine metabolism may be enhanced in depressed patients through these cytokines. Although IL-6 does not directly act on IDO, its elevated levels in serum may contribute to IDO activation within the CNS by the stimulatory effect on PGE2, which acts as cofactor in the activation of IDO. This fits with a report on the correlation of increased in vitro IL-6 production with decreased tryptophan levels in depressed. Due to the increase of proinflammatory cytokines and PGE2 in some psychiatric patients, antiinflammatory treatment would be expected to show advantagous effects in schizophrenic and depressed patients. Cyclo-oxygenase-2 inhibitors have been evaluated in major depression. We were able to demonstrate a statistically significant therapeutic effect of the COX-2 inhibitor on depressive symptoms in a randomized double blind pilot add-on study using the selective COX-2 inhibitor celecoxib in MD. Another randomized double-blind study in fifty depressed patients suffering from MD also showed an statistically significant better outcome of the COX-2 inhibitor celecoxib plus fluoxetine compared to fluoxetine alone. Additionally, results of the clinical study of celecoxib add-on to sertraline and the effects of this anti-inflammatory therapy approach to inflammatory markers planned by the MOODINFLAME consortium will be presented as far as available. Further on, alternative therapeutic strategies based on immune-modulatory effects will be discussed.

Relative Thromboembolic Risks Associated with COX-2 Inhibitors

2005 ◽  
Vol 39 (7-8) ◽  
pp. 1249-1259 ◽  
Author(s):  
S Christopher Jones
Keyword(s):  
Cardiovascular Risk ◽  
Safety Data ◽  
Risk Profile ◽  
Current Evidence ◽  
Cardiovascular Safety ◽  
Cardiovascular Risk Profile ◽  
Double Blind ◽  
Medline Search ◽  
Cox 2 ◽  
Cox 2 Inhibitors

OBJECTIVE To evaluate the clinical literature on cyclooxygenase-2 (COX-2) inhibitors to determine whether a greater incidence of thromboembolic events is universal within the drug class. DATA SOURCES A MEDLINE search was conducted (1996–March 2005) for key articles in the English language assessing the efficacy or safety of these agents. STUDY SELECTION AND DATA EXTRACTION Randomized, double-blind, and controlled trials, as well as case–control and retrospective cohort studies, that assessed the cardiovascular safety of COX-2 inhibitors were reviewed. DATA SYNTHESIS Seventeen published studies were reviewed, and the cardiovascular safety data were extracted from each trial. The mechanism by which COX-2 inhibitors may induce a thromboembolic event is likely multifactorial involving (1) COX-2–specific isoform binding affinity, (2) drug dose, (3) duration of therapy, and (4) cardiovascular risk profile of the patient. Evidence supports an association between cardiovascular adverse events and the use of rofecoxib, valdecoxib, and celecoxib. However, this risk is not equally distributed among the drugs. Given the relative paucity of data, lumiracoxib and etoricoxib cardiovascular effects remain uncertain. CONCLUSIONS Each COX-2 inhibitor has a unique cardiovascular risk profile. Based on the current evidence, celecoxib is the safest COX-2 inhibitor when prescribed appropriately in the lowest possible dose for the shortest duration in the ideal target population.

Comparison of the efficacy of moclobemide and fluvoxamine in elderly patients with a severe depressive episode

1993 ◽  
Vol 8 (6) ◽  
pp. 319-324 ◽  
Author(s):  
JP Bocksberger ◽  
JP Gachoud ◽  
J Richard ◽  
Ρ Dick
Keyword(s):  
Side Effects ◽  
Elderly Patients ◽  
Psychomotor Retardation ◽  
Antidepressant Effect ◽  
Reversible Inhibitor ◽  
Double Blind Study ◽  
Double Blind ◽  
New Class ◽  
Low Incidence ◽  
To Receive

SummaryIn a double-blind study carried out on elderly patients (older than 65 years) the efficacy and tolerability of the new antidepressant moclobemide was compared. Moclobemide belongs to a new class of substances called RIMA (Reversible inhibitor of the monoamine oxidase type A). Fluvoxamine, a selective reuptake-inhibitor of 5-HT, belongs to a class of antidepressants known for their better tolerability compared to tricyclic especially with elderly patients. Forty elderly patients (mean age 75 years) with major depression (according to DSM III) were randomized to receive either moclobemide (300 mg) or fluvoxamine (100 mg) twice daily. Dosages were increased when necessary on day 8, to a maximum of 450 mg moclobemide or 200 mg fluvoxamine and in most cases were maintained at these levels for the remainder of the study period (four weeks). Moclobemide was more effective than fluvoxamine showing a marked antidepressant effect and an earlier effect on psychomotor retardation. The two drugs were well tolerated showing a low incidence of side effects.

A Double-Blind Out-Patient Trial of Indalpine vs Mianserin

1985 ◽  
Vol 147 (3) ◽  
pp. 306-309 ◽  
Author(s):  
G. J. Naylor ◽  
B. Martin
Keyword(s):  
Side Effects ◽  
Treated Group ◽  
Blind Study ◽  
Antidepressant Effect ◽  
Double Blind Study ◽  
Double Blind ◽  
Significant Difference

SummaryIndalpine 150 mg per day and mianserin 60 mg per day were compared in a double-blind study of 65 depressed out-patients: 52 patients completed the 4-week trial. At the end of four weeks there was no significant difference in antidepressant effect between the two drugs; but in the first two weeks, improvement in the mianserin-treated group was significantly greater than that in the indalpine group. The mianserin-treated group reported more side-effects of sedation (eg. drowsiness, clumsiness, heaviness of limbs etc.) and one patient on indalpine developed a mild leucopenia.

Is COX-2 a ‘collateral’ target in cancer prevention?

2005 ◽  
Vol 33 (4) ◽  
pp. 724-727 ◽  
Author(s):  
K. Kashfi ◽  
B. Rigas
Keyword(s):  
Cancer Prevention ◽  
Malignant Lesion ◽  
Aberrant Crypt Foci ◽  
Cardiovascular Side Effects ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
In Vitro Data ◽  
Modest Effect

NSAIDs (non-steroidal anti-inflammatory drugs) prevent colon and other cancers. The fact that NSAIDs inhibit the eicosanoid pathway prompted mechanistic drug-developmental work focusing on COX (cyclo-oxygenase) and its products. The increased prostaglandin E2 levels and the overexpression of COX-2 in colon and many other cancers provided the rationale for clinical trials with COX-2 inhibitors for cancer prevention or treatment. However, one COX-2 inhibitor has been withdrawn from the market because of cardiovascular side effects, and there are concerns about a class effect. Evidence suggests that COX-2 may not be the only, or the ideal, target for cancer prevention; for example, COX-2 is not expressed in human aberrant crypt foci, the earliest recognizable pre-malignant lesion in the colon; COX-2 is expressed in less than half of the adenomas; in vitro data show that NSAIDs do not require the presence of COX-2 to prevent cancer; in familial adenomatous polyposis, the COX-2 inhibitor, celecoxib, had a modest effect, which was weaker than that of a traditional NSAID; and COX-2-specific inhibitors have several COX-2-independent activities, which may account for part of their cancer-preventive properties. The multiple COX-2-indpendent targets, and the limitations of COX-2 inhibitors, suggest the need to explore targets other than COX-2.

Therapeutic Effect of Ticlopidine, a New Inhibitor of Platelet Aggregation, on Chronic Arterial Occlusive Diseases, a Double-blind Study versus Placebo

Angiology ◽  
1982 ◽  
Vol 33 (6) ◽  
pp. 357-367 ◽  
Author(s):  
Tatsuki Katsumura ◽  
Yoshio Mishima ◽  
Kisaku Kamiya ◽  
Shukichi Sakaguchi ◽  
Tatsuzo Tanabe ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Therapeutic Effect ◽  
Blind Study ◽  
Double Blind Study ◽  
Double Blind ◽  
Arterial Occlusive Diseases
Sign in / Sign up

Export Citation Format

Share Document