1D polymeric platinum cyanoximate: a strategy toward luminescence in the near-infrared region beyond 1000 nm.

We report the synthesis and properties of the first representative of a new class of PtL2 complexes with ambidentate mixed-donor cyanoxime ligands [L = 2-cyano-2-oximino-N,N'-diethylaminoacetamide, DECO (1)]. Three differently colored polymorphs of "Pt(DECO)2" (3-5) were isolated, with the first two being crystallographically characterized. The dark-green complex [Pt(DECO)2]n (5) spontaneously forms in aqueous solution via aggregation of yellow monomeric complex 3 into the red dimer [Pt(DECO)2]2 (4), followed by further oligomerization into coordination polymer 5. A spectroscopic and light-scattering study revealed a "poker-chips"-type 1D polymeric structure of 5 in which units are held by noncovalent metallophilic interactions, forming a Pt---Pt wire. The polymer 5 shows a broad absorption at 400-900 nm and emission at unusually long wavelengths in the range of 1000-1100 nm in the solid state. The near-infrared (NIR) emission of polymer 5 is due to the formation of a small amount of nonstoichiometric mixed-valence Pt(II)/Pt(IV) species during synthesis. A featureless electron paramagnetic resonance spectrum of solid sample 5 recorded at +23 and -193 °C evidences the absence of Pt(III) states, and the compound represents a "solid solution" containing mixed-valence Pt(II)/Pt(IV) centers. Exposure of KBr pellets with 5% 5 to Br2 vapors leads to an immediate ∼30% increase in the intensity of photoluminescence at 1024 nm, which confirms the role and importance of mixed-valence species for the NIR emission. Thus, the emission is further enhanced upon additional oxidation of Pt(II) centers, which improves delocalization of electrons along the Pt---Pt vector. Other polymorph of the "Pt(DECO)2" complex--monomer--did not demonstrate luminescent properties in solutions and the solid state. An excitation scan of 5 embedded in KBr tablets revealed an emission only weakly dependent on the wavelength of excitation. The NIR emission of quasi-1D complex 5 was studied in the range of -193 to +67 °C. Data showed a blue shift of λmax and a simultaneous increase in the emission line intensity with a temperature rise, which is explained by analogy with similar behavior of known quasi-1D K2[Pt(CN)4]-based solids, quantum dots, and quantum wells with delocalized carriers. The presented finding opens a route to a new class of platinum cyanoxime based NIR emissive complexes that could be used in the design of novel NIR emitters and imaging agents.

Differences in medication adherence and healthcare resource utilization patterns: older versus newer antidepressant agents in patients with depression and/or anxiety disorders.

BACKGROUND: Given the number of antidepressants available and their rising costs, healthcare payers have initiated restrictive reimbursement policies for newer antidepressants, without consideration for differences in their effectiveness or tolerability. OBJECTIVE: The objective of this study was to comprehensively compare medication adherence rates and associated healthcare utilization costs for patients using later-generation versus earlier-generation antidepressants in a managed care setting. Antidepressants launched after 2002 were deemed third-generation antidepressants, while antidepressants available prior to 2002 were deemed first-generation (TCAs and MAOIs) and second-generation (serotonin and noradrenaline [norepinephrine]-dopamine reuptake inhibitors). STUDY DESIGN: Retrospective database analysis using medical and pharmacy data from over 75 managed care plans covering 55 million lives. SETTING/PATIENTS: All patients receiving an antidepressant between 1 January 2002 and 30 September 2004 were identified. The index date for patients was the date of their first antidepressant prescription within this time period. Patients had to (i) have a diagnosis of depression or anxiety disorder, or depression and anxiety disorder within 6 months prior to or 30 days after their index prescription; (ii) be at least 18 years of age, without having taken antidepressant therapy for 6 months prior to their index date; and (iii) be continuously eligible for 6 months prior to their index date and during their 6-month follow-up period. Patients were excluded if they had a diagnosis of psychosis-related disease, Alzheimer's or Parkinson's disease, or were initiated on psychosis-related medications. INTERVENTION/MAIN OUTCOME MEASURE: Patients meeting selection criteria were followed for 6 months to assess rates of antidepressant adherence, therapy change rates and medical healthcare costs. STUDY POPULATION: A total of 266 665 patients met the study criteria. Approximately 66% were female, with a mean age of 39 years. About 63% had a diagnosis of depression, 31% had an anxiety disorder diagnosis and 6% had diagnoses for both an anxiety disorder and depression. Therapy change: Therapy change within 6 months occurred in 18% of patients receiving third-generation agents compared with 21% and 40% for second- and first-generation agents, respectively. The odds of a therapy change were significantly lower with third-generation antidepressants compared with both older agent cohorts. Adherence: Of patients receiving third-generation antidepressants, 33.6% were adherent compared with 29.3% and 12.4% of patients receiving second- and first-generation antidepressants, respectively. Newer agents also had better adherence rates across all diagnostic cohorts. After adjusting for baseline differences, the odds of being adherent to therapy were significantly lower for those taking second- and first-generation agents versus newer antidepressants. Among the newer agents, the proportion of patients adherent to their therapy was: venlafaxine extended release 38%, paroxetine controlled release (CR) 35%, escitalopram 34%, duloxetine 32% and bupropion extended release (XL) 31%. Healthcare utilization: Of the patients taking older antidepressants, 13% (second generation) and 21% (first generation) were hospitalized at least once for any reason compared with 12% of patients taking newer agents. Overall, the odds of all-cause hospitalization within 6 months of therapy initiation were significantly higher for patients taking older antidepressants. Among the newer agents, hospitalization rates ranged from 15.9% for duloxetine to 12.5% for paroxetine CR and bupropion XL. The unadjusted 6-month total medical costs (not including pharmacy costs) per patient were $US 3514 for second-generation, $US 5744 for first-generation and $US 3284 for newer antidepressants. After controlling for baseline differences, patients receiving second- and first-generation antidepressants incurred 12% and 44% higher costs, respectively. The unadjusted 6-month medical costs for the newer agents ranged from $US 2715 for paroxetine CR to $US 6042 for duloxetine. CONCLUSION: The results of this study provide essential information for healthcare decision makers about the potential advantages of newer generation antidepressants versus older generation antidepressants, as well as the differences between the specific newer agents, with respect to improved rates of adherence and therapy change, reduced hospitalizations and healthcare costs.

Differences in compliance patterns across the selective serotonin reuptake inhibitors (SSRIs).

OBJECTIVE: To evaluate differential compliance rates between immediate-release (IR) selective serotonin reuptake inhibitors (SSRI) and a controlled-release (CR) SSRI in patients initiating SSRI therapy. METHODS: A retrospective analysis of patients initiating treatment with SSRIs identified in the IHCIS National Managed Care Database between July 2001 and December 2002 was conducted. Logistic regression models were used to assess differences in 6-month compliance rates, controlling for age, gender, utilization of mental health specialty care services, titration rates, diagnoses, and comorbidities. Compliance was defined as having a minimum medication possession ratio of 80% over a 180-day period without evidence of a 15-day gap prior to 90 days of therapy. RESULTS: There were 116 090 patients included in the study, with approximately 4% receiving a CR SSRI and 96% receiving IR SSRIs. Approximately 25% of patients had a diagnosis for depression, 16% had a diagnosis for anxiety, and 13% had a 16% had a diagnosis for anxiety, and 13% had a diagnosis for both anxiety and depression. Overall, diagnosis for both anxiety and depression. Overall, 54.2% were noncompliant with therapy, while 30.2% of patients were compliant with therapy, and 15.7% had evidence of a therapy change. After controlling for baseline covariates, patients initiating IR SSRIs were 14% less likely to be compliant compared to those initiating paroxetine CR (p < 0.0001). Patients initiating on paroxetine IR were least likely to be compliant (odds ratio [OR] 0.788; p < 0.0001), followed by escitalopram (OR 0.850; p = 0.0179), sertraline (OR 0.877; p = 0.0005), citalopram (0.909; p = 0.0114), and fluoxetine (OR 0.916; p = 0.0250). CONCLUSIONS: Approximately 54% of patients initiating SSRI therapy were noncompliant with SSRI therapy over a 6-month period, with the lowest level of compliance found in patients receiving IR SSRI agents. Future studies should assess the effect of compliance on economic measures and determine if reductions in resource utilization are found across specific SSRI agents.

Adherence to paroxetine CR compared with paroxetine IR in a Medicare-eligible population with anxiety disorders.

There are many challenges in the pharmacologic management of elderly patients with anxiety disorders, including an increased sensitivity to drug effects, reduced drug metabolism, and socioeconomic barriers leading to poor medication adherence. As such, the purpose of this study was to evaluate differential rates of adherence between paroxetine controlled release (CR) and paroxetine immediate release (IR) in the treatment of anxiety disorders in a Medicare-eligible population. Patients aged 65 years or older initiating therapy with paroxetine CR or paroxetine IR with a diagnosis of anxiety were identified from the Integrated Healthcare Information Services National Managed Care Benchmark database from July 2001 to February 2004. Logistic regression models were used to assess differences in 6-month adherence rates, controlling for differences in multiple background characteristics. Adherence was defined as having a minimum medication possession ratio of 80% over 180 days without evidence of a 15-day gap before 90 days of therapy. Of the 604 patients included in the study, 18% received paroxetine CR and 82% received paroxetine IR; comorbid anxiety and depression were present in 37.3% of patients. Overall, only 37.3% of patients adhered to therapy, with a greater percentage of patients adhering to paroxetine CR (45.0%) compared with paroxetine IR (35.6%). After controlling for background characteristics, patients receiving paroxetine IR were 38.7% less likely to adhere to therapy compared with patients receiving paroxetine CR (P = .0328). When stratified by those with comorbid anxiety and depression, patients receiving paroxetine IR were 55.1% less likely to adhere to therapy compared with patients receiving paroxetine CR (P = .0292). This study demonstrates that antidepressant nonadherence is common in patients older than 65 years of age, with overall rates of nonadherence at 62.7% and patients receiving paroxetine IR having the lowest levels of adherence. Future work should assess differences in all available selective serotonin reuptake inhibitors while also directly assessing the economic impact of nonadherence in the elderly population.

Rate of non-adherence prior to upward dose titration in previously stable antidepressant users.

BACKGROUND: Non-adherence to antidepressant medications is a contributing factor to disease relapse and may result in needless increases in antidepressant dosing. METHODS: We analyzed de-identified patient claims data from Medco Health Solutions, Inc.'s information database and measured adherence as the medication possession ratio (MPR), with adequate adherence as MPR ≥80%. Adherence was calculated for patients in whom antidepressants were dose escalated and who were on the same antidepressant medication for at least 180 days before the upward dosage titration. Statistical analysis was performed on subgroups comparing adherence with mail vs. retail channels, differences in age and gender, generic prescription vs. brand only, and prescription by psychiatrist vs. non-psychiatrist. RESULTS: 29.7% of patients were non-adherent to their antidepressant medication during the 6 months prior to a prescribed increase in dosage. Non-adherence was significantly lower among patients using the Medco Therapeutic Resource Centers® mail order vs. retail channel. Younger age correlated with poorer adherence. Rates of non-adherence were also significantly greater among women, those receiving generic medications, and among patients with overall lower disease comorbidity. Adherence was not significantly impacted by prescription from a psychiatrist or a non-psychiatrist. LIMITATIONS: Retrospective design and use of an administrative patient claims database. CONCLUSIONS: Suboptimal medication adherence commonly precedes an upward dosage titration of antidepressant medications. Utilization of a mail order channel may improve adherence. Clinicians prescribing antidepressants should explore adherence issues carefully prior to recommending an increase in dosage.