Rapamycin Has Biological Activity in a Subset of Patients with Myelodysplastic Syndrome - Results of a Phase I/II Trial.

Abstract The pathophysiology of myelodysplastic syndrome (MDS) involves disturbed regulation of angiogenesis, apoptosis, proliferation and differentiation as well as immune surveillance. There is increasing evidence that rapamycin (sirolimus) might affect these pathways positively thus possibly being of therapeutic benefit in patients with this disease. These data prompted us to perform a phase I/II study to evaluate the safety and efficacy of rapamycin in the treatment of patients with MDS. Nineteen patients (median age 72 years) diagnosed with MDS according to the WHO classification received rapamycin orally with a target blood concentration of 3–12 ng/ml. Rapamycin was administered for a median of 3.7 months (range 0.3–11). Three patients (1 x RAEB-2, 1 x RAEB-1, 1 x RCMD) showed either a major (1 x platelet, 1 x neutrophil) or a minor (1 x erythroid, 2 x platelet) hematological response according to the IWG criteria. There was no statistically significant difference in the rapamycin plasma levels between the three responders (median plasma level 3.62, range 1.63–4.39) and non-responders (median plasma level 4.22, range 2.81–7.4). Major side effects were hyperlipidemia (n=4), stomatitis (n=3), thrombocytopenia (n=2) and urinary tract infection (n=1). Study medication had to be stopped due to side effects in five patients (26 %), one of them being a responder to rapamycin. Plasma levels of rapamycin were not elevated in patients experiencing toxicity. Taken together these data demonstrate that rapamycin might have biological activity in patients with rather advanced MDS. New and possibly less toxic analogues of rapamycin are currently developed. They could be candidates for future trials in patients with MDS.

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What Does Antidepressant Drug level Monitoring Reveal About Outpatient Treatment and Patient Adherence?

Pharmacopsychiatry ◽

10.1055/s-0044-101838 ◽

2018 ◽

Vol 52 (02) ◽

pp. 78-83 ◽

Cited By ~ 3

Author(s):

Petr Silhan ◽

Romana Urinovska ◽

Ivana Kacirova ◽

Martin Hyza ◽

Milan Grundmann ◽

...

Keyword(s):

Plasma Level ◽

Outpatient Treatment ◽

Plasma Levels ◽

Selective Serotonin Reuptake Inhibitors ◽

Reference Range ◽

Patient Adherence ◽

Antidepressant Drug ◽

Drug Level ◽

Maximum Plasma ◽

Significant Difference

Abstract Introduction The evaluation of plasma levels of antidepressants may improve the treatment outcome. The aim was to verify adherence and adequacy of administered doses of antidepressants among patients hospitalized for inadequate outpatient therapeutic response. Methods Selective serotonin reuptake inhibitors or venlafaxine plasma levels were assessed on the first day of hospitalization and after 3 days of controlled administration. The patients were considered adherent if the plasma level on admission was within the interval of the minimum and maximum plasma level on the fourth day, expanded by 30%. The adequacy of antidepressant doses used during the outpatient treatment was assessed by comparing the plasma level on the fourth day with the therapeutic reference range. Results Out of 83 patients, 52 (62.7%) were adherent. The plasma levels of antidepressants on the fourth day were found to be within the therapeutic reference range in 35 (43.2%) patients. The same number manifested levels below the therapeutic reference range. In 11 (13.6%) patients, the levels were higher than recommended. No significant difference in rate of adherence was found among individual antidepressants. Conclusion The results show that antidepressant nonresponders are frequently under-dosed or nonadherent.

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Correlation of New Method for Measuring Plasma Myeloperoxidase with Clinical Behavior in Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Blood ◽

10.1182/blood.v110.11.4321.4321 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4321-4321

Author(s):

Adam Abdool ◽

Xiugiang Wang ◽

Iman Jilani ◽

Weidong Zhou ◽

Hagop Kantargian ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myelodysplastic Syndrome ◽

Plasma Levels ◽

Myeloid Leukemia ◽

Inflammatory Process ◽

Advanced Stage ◽

Clinical Behavior ◽

Significant Variability ◽

Significant Difference ◽

Acute Myeloid

Abstract We previously reported that levels of myeloperoxidase (MPO) enzyme in plasma of patients with acute myeloid leukemia (AML) may correlate with aggressive disease. However, we found poor reproducibility and significant variability from lot to lot when commercially available kits are used. We developed a cytometric beads assay (CBA) for measuring plasma MPO that shows high reproducibility (CV<10%) with no significant variability with time. More importantly, MPO levels as measured using this CBA assay showed better correlation with clinical behavior in AML and myelodysplastic syndrome (MDS). Based on studying plasma levels of MPO in 98 patients with AML and 50 patients with advanced stage MDS, we found no significant difference in plasma MPO between AML and MDS patients. As expected MPO levels were significantly lower in patients with ALL (N=48) than in AML patient (P=0.04) and MDS (P=0.02). While MPO levels were significantly higher in patients with good cytogenetic abnormalities (P=0.004) in AML patients, MPO levels did not differ between intermediate and poor cytogenetic groups in patients with AML or MDS. Unexpectedly we found a difference between AML and MDS in their correlation with MPO levels and clinical outcome. Patients with advanced stage MDS and high levels of MPO (<300 ng/ml) had significantly longer survival than patients with lower levels (P=0.01). Multivariate analysis showed that this correlation with better survival in this group of MDS patients was independent of cytogenetic grouping. In contrast in AML, higher levels of MPO (>70 ng/ml) correlated with shorter survival (P=0.04). Similarly, patients with acute lymphoblastic leukemia (ALL) and high levels of MPO (>70 ng/ml) had shorter survival (P=0.05). Despite there was a correlation between the commercially available kit for measuring MPO and our CBA method (r=0.71, P<0.0001), the commercial kit did not provide robust data for clinical correlation. This data confirms that confirms that plasma levels of MPO play a role in the biology of the leukemia. Further studies are needed to establish if this role is a reflection of an inflammatory process or a reflection of disease load, although the finding of clinical relevance in ALL suggests that it is more likely reflecting an inflammatory process. Figure Figure

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PERBEDAAN KADAR PSA DAN TGF-β1 TERHADAP PEMBERIAN KOMBINASI INHIBITOR 5α-REDUKTASE (DUTASTERIDE) DAN ANTI ESTROGEN (TAMOXIFEN) PADA PASIEN BPH LUTS

Indonesian Journal of Urology ◽

10.32421/juri.v15i2.353 ◽

1970 ◽

Vol 15 (2) ◽

Author(s):

Rachmat Budi Prasetyo ◽

Soetojo Soetojo ◽

Doddy M Soebadi

Keyword(s):

Placebo Group ◽

Plasma Level ◽

Urinary Retention ◽

Plasma Levels ◽

Reductase Inhibitor ◽

Combination Group ◽

Tamoxifen Group ◽

Significant Difference ◽

Before And After ◽

Tgf Β1

Objective: To compare the PSA and TGF-β1 plasma level before and after administration of a 5α-reductase inhibitor (dutasteride) and an anti estrogen (tamoxifen) in nonobstructive patients with BPH. Material and Method: We enrolled 40 patients with a diagnosis of BPH without urinary retention. Patients were allocated into 4 groups of 10 patients and were given tamoxifen, dutasteride, a combination of tamoxifen and dutasteride, or placebo. We measured PSA and TGF-β1 plasma levels at study entry and 3 months after administration. Data were analysed using SPSS 12. Results: Increase of TGF-β1, as high as 54% (2,18 ± 0,88 to 3,36 ± 1,06) in the tamoxifen group, 26% (2,75 ± 0,62 to 3,47 ± 0,82) in the dutasteride group, and 92% (2,37 ± 0,75 to 4,56 ± 1,98) in the combination group, was significant (p < 0,05). PSA was not significantly decreased in all groups (p > 0,05). PSA decreased 28% (4,25 ± 3,28 to 3,06 ± 3,08) in the tamoxifen group, 27% (2,20 ± 2,17 to 1,60 ± 0, 982) in the dutasteride group, and 19% (2,95 ± 1,22 to 2,40 ± 1,78) in the combination group. In the placebo group was no significant difference of both parameters. Conclusion: TGF-β1 was significantly increased in all groups except in placebo. PSA was decreased in all groups but not significant statistically. We concluded that TGF-β1 may better be used as a biomarker in the evaluation and management of BPH than PSA.

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High doses of carbamazepine for refractory partial epilepsy

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x1996000100007 ◽

1996 ◽

Vol 54 (1) ◽

pp. 42-46 ◽

Cited By ~ 1

Author(s):

Cristiana Borges Pereira ◽

Carlos Otto Heise ◽

Arthur Cukiert

Keyword(s):

Side Effects ◽

Plasma Level ◽

Plasma Levels ◽

Partial Epilepsy ◽

The Other ◽

Partial Seizures ◽

High Doses ◽

Higher Doses ◽

Refractory Partial Epilepsy

Forty-eight patients with partial seizures were analysed during treatment with 1200 mg/d or more of carbamazepine (CBZ). Thirty-three were on monotherapy and fifteen on polytherapy. The other drugs were kept unchanged in the patients on polytherapy. The dose of CBZ was increased if no control was observed and the patient had no side effects. The doses used ranged between 1200 and 1900 mg/day (1200 mg/day, n=18; 1300mg/day, n=1; 1400 mg/day, n=7; 1600 mg/day, n=9; 1700 mg/day, n=4; 1800 mg/day, n=8; 1900 mg/day, n=1). Anticonvulsant plasma levels were taken to confirm patient compliance. The average plasma level was 9.6 ug/mL. The period of follow up varied from 3 to 96 months (M=25.6). Seizure's control was observed in 7 (14.48%) patients taking 1200 mg/day and in 2 (4.16%) patients taking 1400 mg/day of CBZ. Thirty-nine patients did not show any control (81.21%). Ten patients (20.81%) had signs of intoxication. When patients have no improvement with 1400 mg/day, it is difficult to obtain any control despite the use of higher doses of CBZ, which frequently expose the patient to significant side effects.

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The Plasma Levels of Dehydroepiandrosterone Sulfate Are Decreased in Patients with Chronic Heart Failure in Proportion to the Severity*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.85.5.6568 ◽

2000 ◽

Vol 85 (5) ◽

pp. 1834-1840 ◽

Cited By ~ 2

Author(s):

Yasushi Moriyama ◽

Hirofumi Yasue ◽

Michihiro Yoshimura ◽

Yuji Mizuno ◽

Koichi Nishiyama ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Chronic Heart Failure ◽

Plasma Level ◽

Natriuretic Peptide ◽

Plasma Levels ◽

Thiobarbituric Acid ◽

The Elderly ◽

Dehydroepiandrosterone Sulfate ◽

Significant Difference

Abstract Dehydroepiandrosterone sulfate (DHEAS) is the major secretory steroid of the human adrenal glands. The secretion of DHEAS decreases with aging. The incidence of heart failure also rises in the elderly population. We measured the plasma levels of DHEAS and cortisol in 49 patients with chronic heart failure (CHF) and 32 age-matched controls and assessed its relation to plasma levels of A-type natriuretic peptide and B-type natriuretic peptide, biochemical markers of heart failure. Plasma levels of DHEAS were significantly lower in patients with CHF than in controls, whereas there was no significant difference in plasma levels of cortisol between the two groups. In stepwise regression analysis, the plasma level of DHEAS was significantly and independently correlated with age (β = −0.451; P < 0.0001) and the plasma level of B-type natriuretic peptide (β = −0.338; P < 0.001), and the plasma cortisol/DHEAS ratio was significantly and independently correlated with the plasma levels of A-type natriuretic peptide (β = 0.598; P < 0.0001) and thiobarbituric acid-reactive substances (a marker of oxidative stress;β = 0.252; P < 0. 01) and age (β = 0.171; P < 0.05). These results indicate that the plasma levels of DHEAS are decreased in patients with CHF in proportion to its severity and that oxidative stress is associated with decreased levels of DHEAS in patients with CHF.

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The role of asymmetric dimethylarginine (ADMA) in the follow-up of patients with precapillary pulmonary hypertension (PH)

European Heart Journal ◽

10.1093/ehjci/ehaa946.2303 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

I Shafran ◽

V Probst ◽

J Campean ◽

R Sadushi-Kolici ◽

C Gerges ◽

...

Keyword(s):

Pulmonary Hypertension ◽

High Risk ◽

Plasma Level ◽

Plasma Levels ◽

Asymmetric Dimethylarginine ◽

Low Risk ◽

Hemodynamic Assessment ◽

Significant Difference

Abstract Introduction Asymmetric dimethylarginine (ADMA) interferes with L-arginine in the production of nitric oxide, a key mediator of endothelial cell function. ADMA is elevated in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) and is associated with unfavorable outcomes. Aim To assess the role of ADMA to monitor disease progression of PH patients treated with PAH-specific therapy. Methods ADMA was measured by competitive ELISA at baseline (BL) and follow-up (FU). Risk assessment including a clinical assessment, echocardiography, 6-minute walking test, NT-pro-BNP and hemodynamic assessment by right heart catheterization was performed accordingly. Risk was calculated according to the ESC/ERS 2015 guidelines by the SPHAR method. Results ADMA samples were collected from 113 patients treated at our institution between 2012 and 2019. 89 (79%) patients had PAH, 15 (13%) were diagnosed with CTEPH and 9 (8%) with group 3 – PH associated with lung disease. 69% were females. 15 (13.3%) patients had a low risk at baseline, 96 (85%) intermediate risk and 2 (1.8%) were high risk patients. 75% received oral medications, 31% received subcutaneous treprostinil. Median baseline ADMA was 0.738umol/l. At BL no significant difference of ADMA plasma levels was found among the different PH types (p=0.063), or between different risk categories (p=0.531). Change in ADMA plasma levels correlated with change in risk (p=0.002, rs 0.291) and with change in mixed venous saturation (p=0.034, rs −0.205). Change in ADMA plasma levels also correlated with risk at FU (p=0.011, rs 0.240). Patients categorized as low risk at FU had a median ADMA plasma level decrease of 22%, compared with −3 to 0% ADMA plasma level change in patients with moderate to high risk at FU (p=0.04). Patients who improved their risk category had a median decrease of ADMA plasma level of 23% vs. 2.3% in patients who did not improve (p=0.011). Decrease of ADMA plasma levels was a weak but significant discriminator for improvement of risk in ROC analysis (p=0.032, AUC 0.374). Conclusion ADMA plasma levels paralleled the hemodynamic and clinical benefit of PAH-specific treatments in patients with precapillary PH. ADMA could be used as a biomarker for monitoring treatment effects in precapillary PH. Funding Acknowledgement Type of funding source: None

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A Comparison of Efficacy Between Recombinant Activated Factor VII (ARYOSEVEN TM) and NOVOSEVEN® in Patients with Hereditary FVIII Deficiency with Inhibitor

Blood ◽

10.1182/blood.v124.21.4299.4299 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4299-4299 ◽

Cited By ~ 1

Author(s):

Mohammad Faranoush ◽

Hassan Abolghassemi ◽

Gh Toogeh ◽

Mehran Karimi ◽

Peyman Eshghi ◽

...

Keyword(s):

Plasma Level ◽

Hemophilia A ◽

Treatment Success ◽

Factor Vii ◽

Global Response ◽

Significant Difference ◽

Median Plasma ◽

Group A ◽

Bleeding Episodes ◽

Group B

Abstract Introduction: Concentrated factor VIII replacement therapy in severe hemophilia prevents disabling arthropathy, life-threatening bleeding, improves health related quality of life and increase life expectancy. Patients with neutralizing antibodies (inhibitors) did not respond to usual doses of FVIII and they need higher doses of FVIII or bypassing agents (eg. rFVIIa, FEIBA) to control bleeding. The aim of this study was to compare the efficacy of a new biosimilar recombinant factor VIIa (Aryoseven ™) with Novoseven® in controlling bleeding episodes in hemophilia A patients with inhibitors. Methods: A randomized double blind clinical trial study was conducted in eight comprehensive hemophilia care centers in Iran. We randomized 66 male patients in two groups, with 4 consecutive block randomization when bleeding occurred. All patients entered the study with only one bleed. Informed consent signed by all patients or their parents. Group A (31 patients, 47%) received Aryoseven ™ and group B (35 patients, 53%) received Novoseven®. rFVIIa dosage was 90 -120 μg/kg intravenously every 2 hours. Results: During the study 66 patients (All male) were enrolled in two arms. The mean age was 20.5±10.9 years. Comparison of baseline data between the two showed no significant difference. The distributions of these variables were similar between the two groups. Other factors, such as vital signs, coagulation tests, liver, renal function tests, and blood count were not significantly different between the two groups. Median plasma level of FVII clotting activity (FVII: C) in group A and B was 103.8±38.4 IU/ dl and 98.6±26.7 IU/dl before injection respectively. Median plasma level of FVIII inhibitor in group A and B was 15.0 BU (IQR: 8.8-58.0) and 19.0 BU (IQR: 11.0-31.0). The average time from onset of bleeding to start treatment were 1246± 1104 and 2301 ± 1693 minutes (p = 0.311) in group A and B respectively. This study results showed that increased levels of factor VII were comparable between two groups after rFVIIa injection. A comparison of the Kavakli global response scores after injection and the treatment success rate in terms of achieving to score 6 or higher showed that both groups were comparable in treatment success rates. The global treatment response rate was 96.8% in group A and 91.4% in group B. Administration of either Aryoseven™ or Novoseven® had comparable effect on controlling pain and joint mobility. Reported side effects were minor (headache, nausea, and rash) and occurred in similar frequency. Discussion: The present study showed increased FVII levels and clinical efficacy in the control of the bleeding episodes in Hemophilia A patients with inhibitor for both drugs. Some similarities exist between our findings and the previous clinical trials designed for Novoseven®. In other studies, the treatment success rate by using the global response scoring system has been 70% -86% by different rFVIIa dosage regimen, in our study was above 90% in both treatment groups. In most studies, it was reported more than 90% achieving to cessation of bleeding at 9 hours after first injection of rFVIIa as response time which was also similar to our study. Conclusion: This study showed non-inferiority of Aryoseven ™ compared to Novoseven® in cessation of bleeding episodes in hemophilia A patients with inhibitor. There was no evidence of significant difference between the efficacy and safety of two drugs. There were no clinically meaningful differences between the biosimilar product and the original product in terms of the safety, purity, and efficacy. Biosimilar rFVIIa is effective in treatment of acute joint bleeding in patients with inhibitor in comparison to Novoseven®. Disclosures Mehrvar: Aryogen Zist Darou: Employment. Khoein:Aryogen Zist Darou: Employment. Kaymar:Aryogen Zist Darou: Employment. Mahbodi:Aryogen Zist Darou: Employment. Vaziri:Aryogen Zist Darou: Employment.

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Variation in dose and plasma level of lamotrigine in patients discharged from a mental health trust

Therapeutic Advances in Psychopharmacology ◽

10.1177/2045125316672573 ◽

2016 ◽

Vol 7 (1) ◽

pp. 17-24 ◽

Cited By ~ 7

Author(s):

Petrina Douglas-Hall ◽

Olubanke Dzahini ◽

Fiona Gaughran ◽

Ahmed Bile ◽

David Taylor

Keyword(s):

Mental Health ◽

Plasma Level ◽

Plasma Levels ◽

Enzyme Inhibitor ◽

Smoking Status ◽

Plasma Concentrations ◽

Significant Difference ◽

The Mean ◽

Health Trust ◽

Enzyme Inducers

Background: The objectives of this study were to investigate the dose of lamotrigine when prescribed with an enzyme inhibitor or enzyme inducer in patients discharged from a mental health trust and to determine the corresponding lamotrigine plasma concentrations and the factors that may affect these. Methods: All patients discharged on lamotrigine between October 2007 and September 2012 were identified using the pharmacy dispensing database. We recorded demographic details, lamotrigine dose and plasma levels and coprescribed medication. Results: During the designated period, 187 patients were discharged on lamotrigine of whom 117 had their plasma levels recorded. The mean lamotrigine daily dose was 226.1 mg (range 12.5–800 mg) and the mean plasma level 5.9 mg/l (range 0.8–18.1 mg/l). Gender, ethnicity, diagnosis and smoking status had no significant effect on dose or plasma levels. Patients taking an enzyme-inducing drug ( n = 6) had significantly lower plasma levels [mean (SD) 3.40 (1.54) mg/l] than those not taking enzyme inducers [ n = 111; 6.03 (3.13) mg/l; p = 0.043]. Patients taking an enzyme-inhibiting drug ( n = 23) had significantly higher levels [7.47 (3.99) mg/l] than those not taking an inhibitor [ n = 94; 5.52 (2.75) mg/l; p = 0.035]. No significant difference was found between the doses of lamotrigine in patients taking an enzyme inhibitor and those not taking one ( p = 0.376). No significant difference was found between the doses of lamotrigine in patients taking an enzyme-inducing drug and those not taking any ( p = 0.574). Conclusions: Current dosing recommendations indicate that lamotrigine doses should be halved in individuals taking enzyme inhibitors and doubled in those on enzyme inducers. In our survey these recommendations were rarely followed with the consequence that patients received too high or too low a dose of lamotrigine, respectively.

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“Was it worth it?” A pilot study of advanced cancer patients’ retrospective perceptions of benefit from phase I trial participation

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.19670 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 19670-19670

Author(s):

J. Y. Bruce ◽

F. J. Hlubocky ◽

C. K. Daugherty

Keyword(s):

Quality Of Life ◽

Pilot Study ◽

Side Effects ◽

Phase I ◽

Phase I Trial ◽

Therapeutic Benefit ◽

Trial Participation ◽

Close Monitoring ◽

Retrospective Perceptions

19670 Background: Subjects who enroll in phase I cancer trials generally are those with advanced and terminal disease. Although all such patients (pts) undergo an informed consent process, there is evidence that these pts may not appreciate the primary aims of a phase I trial and have unrealistic expectations of therapeutic benefit. However, these perceptions of benefit have not been described in pts after trial enrollment. Methods: As a pilot study, pts previously enrolled on Phase I trials were interviewed regarding their retrospective perceptions of benefit. A total of 9 pts have been interviewed to date: median age: 72 yr (range: 59–82 yr); 55% male; 77% Caucasian. The interview included open-ended questions assessing patient experiences with the trial, including reasons for enrollment, impressions of quality of life, costs incurred, and other benefits. Pts’ qualitative responses were recorded and analyzed for content and themes. Results: Reasons for enrollment included hope, prior treatment failure, altruism, and family influence. Described perceptions of anticipated benefit included stabilization of disease and close monitoring of their disease. Unexpected costs involved time spent during clinic visits, financial costs, time taken off work by family members, time spent away from family, and additional trial procedures. Issues of quality of life revolved around side effects from the investigational agent. Many interviewed pts (44%) described improved quality of life off the trial as compared to during trial participation. The majority of interviewed pts (67%) believed that the trial had no effect on their survival. Conclusions: Our data suggest that pts’ perceptions of therapeutic benefit after trial enrollment may be different from pre-enrollment expectations. There would also appear to be potentially significant and otherwise undescribed out-of-pocket expenses incurred by subjects as a result of phase I enrollment. Further research is needed to examine how side effects, unexpected costs, and lack of improved survival contribute to these pts’ perceptions of trial benefit. No significant financial relationships to disclose.

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Large Variations of Plasma Levels During Maintenance Treatment with Depot Neuroleptics

The British Journal of Psychiatry ◽

10.1192/bjp.169.5.618 ◽

1996 ◽

Vol 169 (5) ◽

pp. 618-621 ◽

Cited By ~ 15

Author(s):

Eva Tuninger ◽

Sten Levander

Keyword(s):

Side Effects ◽

Plasma Level ◽

Plasma Levels ◽

Clinical Effect ◽

Clinical Symptoms ◽

Repeated Measurements ◽

Neuroleptic Treatment ◽

Neuroleptic Medication ◽

Depot Neuroleptics ◽

Depot Neuroleptic

BackgroundStability of neuroleptic medication has been associated with optimal clinical effect and minimal side-effects. Depot administration is assumed to yield better stability.MethodThirty patients on depot neuroleptic treatment were followed during three years with repeated measurements of plasma level and concurrent ratings of clinical symptoms and side-effects.ResultsOf 120 blood samples 35 (29%) measurements were outside ± 2 s.d. measurement error (expected 5%). Perphenazine levels were more variable (46%) than haloperidol (25%) and flupenthixol (12.5%). No relationship was found between side-effect ratings and fluctuations of plasma levels.ConclusionDepot neuroleptic medication does not eliminate a clinically unwanted and sometimes marked variation in plasma level.

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