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Biomedical subjects

J M Perel

Publications and source records attributed to J M Perel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Treatment of 70(+)-year-olds with recurrent major depression. Excellent short-term but brittle long-term response.

The authors compared response rates, by age (60-69 vs. 70+), to acute, continuation, and 1-year maintenance depression treatment. Patients (N = 180) received open combined treatment with nortriptyline (NT)/placebo and interpersonal psychotherapy (IPT). Patients who recovered then entered randomized, double-blind maintenance treatment with NT or placebo or received maintenance monthly IPT (combined with NT or placebo). Comparison of time-to-remission and recovery and absolute rates of remission, relapse, recovery, and recurrence yielded similar times to/rates of remission and recovery; however, older patients had far more recurrence during the first year of maintenance therapy. Although responses to acute and continuation treatment with combined NT and psychotherapy were similar, the older group had more recurrence in the first year of maintenance. Continuation of combined medication and psychotherapy may represent the best long-term treatment.

Age Factors↗
PubMed1998

Gauging the effectiveness of extended imipramine treatment for panic disorder with agoraphobia.

BACKGROUND: Imipramine has proven efficacy for panic disorder. This study assesses the net effectiveness of systematic, open imipramine treatment in a homogenous sample of panic disorder patients with agoraphobia. METHODS: One hundred and ten consecutive patients with DSM-III-R moderate to severe panic disorder with agoraphobia were treated with a fixed regimen of imipramine 2.25 mg/kg/day for 24 weeks. No instructions or encouragement for self-directed exposure to phobic situations or other coping strategies with panic or fear were given. Assessments were conducted at the end of the 2-week placebo run-in and at weeks 8, 16, and 24 of treatment. RESULTS: Overall, 53% had a marked and stable response. Most measures revealed that substantial improvement continued beyond week 8 of treatment. Treatment success was accompanied with significant improvements in anxiety sensitivity, dysphoric mood, and functional well-being. CONCLUSIONS: These results provide a clinically relevant reference with which to compare the effectiveness of alternative treatments in providing nearly complete symptom remission in patients with primary panic disorder with agoraphobia.

Adolescent↗
PubMed1998

Asymmetric synthesis and pharmacology of methylphenidate and its para-substituted derivatives.

We report the first asymmetric synthesis of the individual enantiomers of methylphenidate (1). From d-pipecolic acid, the (2R,2'R) and (2S,2'R) enantiomers of 1 were obtained in > 99% optical purity while the (2S,2'S) and (2R,2'S) enantiomers of 1 were derived from l-pipecolic acid in 96% optical purity. The versatility of this methodology is demonstrated with the synthesis of the (2R,2'R) and (2S,2'S) enantiomers of p-bromo and p-methoxy derivatives in similar yields and enantiomeric purities. Comparative neurochemical assessments of these synthesized enantiomers at purported dopamine, norepinephrine, and serotonin uptake sites along with locomotor activity studies in rats are also reported.

Animals↗
PubMed1998

Serum levels of valproate and carbamazepine in breastfeeding mother-infant pairs.

Few data are available about the use of anti-convulsants during breastfeeding. In this article, three women with bipolar disorder who insisted upon breastfeeding their infants were studied. One mother was treated with carbamazepine (CBZ) and two were treated with valproate (VLP) monotherapy. Mother and infant serum levels were assessed when maternal steady-state was reached. The infant whose mother took CBZ developed a serum level that was 15% of the total maternal CBZ. Free CBZ was 20% of maternal values. The two infants whose mothers took VLP developed low serum levels (1.5 and 6.0% of maternal values). In the series, the serum levels of both CBZ and VLP were lower than previously reported values. However, information is limited and careful monitoring is recommended.

Adult↗
PubMed1998

Inverse relationship between fenfluramine-induced prolactin release and blood pressure in humans.

Although substantial evidence from experimental animals suggests that augmentation and reduction in serotonergic neurotransmission both affect arterial blood pressure (BP), it is unknown whether "tonic" central serotonergic activity is related to resting BP variability in humans. We tested this hypothesis in a community sample by evaluating the relationship between resting BP and a neuropharmacologic index of brain serotonergic activity (the fenfluramine challenge test). Subjects were 270 generally healthy men and women aged 25 to 60 years who were not receiving prescribed antihypertensive or psychotropic medications. The sample included 216 non-Hispanic whites and 47 blacks. Resting systolic BP ranged from 85 to 161 mm Hg and diastolic from 58 to 98 mm Hg. Each subject received 0.55 to 0.65 mg/kg D,L-fenfluramine hydrochloride, and the plasma prolactin concentration was measured over 3.5 hours. Analyses revealed a linear, inverse relationship between the maximum fenfluramine-induced prolactin rise and systolic and diastolic BP in whites: r=-0.36 and r=-0.29, respectively (P<0.001 for both). These relationships were not observed in the black participants. In whites, the prolactin response to fenfluramine remained a significant predictor of systolic and diastolic BPs in multivariate models including age, gender, body mass index, physical activity, smoking, and alcohol consumption (P</=0.001). When compared with subjects in the highest quartile of prolactin response, individuals whose prolactin responses to fenfluramine comprised the lowest quartile were 2.6 times more likely to have a resting systolic/diastolic BP of >135/85 mm Hg. These data reveal that in white but not black adults, fenfluramine-induced prolactin release correlates inversely with BP and may indicate a role of central serotonergic activity in the pathogenesis of hypertension.

Adult↗
PubMed1998

Serum sertraline and N-desmethylsertraline levels in breast-feeding mother-infant pairs.

OBJECTIVE: The authors' goal was to study the serum sertraline levels of breast-feeding mothers and their infants. METHOD: They obtained serum levels of sertraline and N-desmethylsertraline in nine mother-infant pairs. RESULTS: Sertraline levels were very low (less than 2 ng/ml) in seven of the nine infants and low (3 ng/ml) in one. N-Desmethylsertraline levels were also low (6 ng/ml or less) in seven of the nine infants. One infant had a high level of N-desmethylsertraline, and one infant had unusual serum sertraline and N-desmethylsertraline values (half of its mother's levels). All infants were thriving. CONCLUSIONS: Most breast-feeding infants whose mothers were taking sertraline had very low serum levels of both sertraline and N-desmethylsertraline, consistent with published reports. The authors discuss in detail the one infant with unusually high levels.

1-Naphthylamine↗
PubMed1998

Effects of age at onset of first lifetime episode of recurrent major depression on treatment response and illness course in elderly patients.

OBJECTIVE: The goal of this study was to examine treatment outcome differences in relation to age at onset of first lifetime episode of recurrent major depression in elderly patients. METHOD: Patients were grouped as having early-onset (N = 129) or late-onset (N = 58) depression. Early onset was defined as having a first lifetime episode of major depression at age 59 or earlier; late onset was defined as age 60 or later. The two groups of patients were compared with respect to demographic and clinical characteristics, types of treatment given (nortriptyline and interpersonal psychotherapy), and treatment outcomes. RESULTS: The groups did not differ in the percentage of patients who remitted, recovered, or relapsed during continuation treatment or in the percentage who experienced a recurrence of major depression during the first year of maintenance treatment. However, early-onset patients took 5-6 weeks longer to achieve remission than did late-onset patients, and a higher proportion had a history of suicide attempts. CONCLUSIONS: These data suggest that age at lifetime onset of recurrent major depression does not influence short- or long-term treatment response in elderly patients treated with combined interpersonal psychotherapy and nortriptyline, with the exception of slowing the speed of remission in early-onset cases. Difference in remission speed may reflect the greater number of previous episodes in the early-onset patients. Nevertheless, the likelihood of a longer time to remission, together with a higher rate of past suicide attempts, suggests that elderly depressed patients with a history of early-onset illness need particularly careful management.

Age Factors↗
PubMed1998

How common is resistance to treatment in recurrent, nonpsychotic geriatric depression?

OBJECTIVE: Effective treatments are available for major depressive disorder in later life. The purpose of this study was to elucidate the frequency of treatment resistance among the elderly. METHOD: Treatment resistance, defined as lack of recovery despite combined pharmacotherapy and psychotherapy, was prospectively examined in 180 elderly patients in an episode of recurrent, nonpsychotic major depression who were referred to a university medical center for treatment. They received open acute and continuation treatment with nortriptyline and interpersonal psychotherapy. RESULTS: Among the 159 patients who completed acute treatment, 19 (11.9%) did not experience a remission of depression. In addition, nine patients who had achieved remission relapsed during continuation therapy and did not recover despite vigorous treatment. Hence, excluding dropouts, 18.4% of the patients met the criteria for treatment resistance by their lack of response to acute treatment or by relapsing during continuation therapy and not recovering subsequently despite further vigorous treatment. CONCLUSIONS: The study suggests a relatively low rate of resistance to treatment among depressed geriatric patients referred to a university tertiary care setting.

Academic Medical Centers↗
PubMed1998

Fluoxetine versus placebo in depressed alcoholic cocaine abusers.

To date, few double-blind, placebo-controlled studies with any selective serotonin reuptake inhibitor (SSRI) antidepressant in pure cocaine abusers or in cocaine abusers with comorbid disorders have been reported. In this study, 17 patients with DSM-III-R diagnoses of major depressive disorder, alcohol dependence, and cocaine abuse were included along with 34 non-cocaine-abusing depressed alcoholics in a pharmacotherapy trial involving the SSRI antidepressant fluoxetine. All 51 patients participated in a double-blind, parallel group study of fluoxetine versus placebo in depressed alcoholics. The principal focus of this article is the one-third of the depressed alcoholics who also abused cocaine and how the treatment response of those 17 patients compared with that of the 34 depressed alcoholics who did not abuse cocaine. During the study, no significant difference in treatment outcome was noted between the fluoxetine group (N = 8) and the placebo group (N = 9) for cocaine use, alcohol use, or depressive symptoms. In addition, no significant within-group improvement was noted for any of these outcome variables in either of the two treatment groups. Indeed, across the combined sample of 17 depressed alcoholic cocaine abusers, the mean Beck Depression Inventory (BDI) score worsened slightly from 19 to 21 during the course of the study, and 71 percent of the patients continued to complain of suicidal ideations at the end of the study. The 17 cocaine-abusing depressed alcoholics showed a significantly worse outcome than the 34 non-cocaine abusing depressed alcoholics on the 24-item Hamilton Rating Scale for Depression (HAM-D) and BDI depression scales and on multiple measures of alcohol consumption. These findings suggest that comorbid cocaine abuse acts as a robust predictor of poor outcome for the drinking and the depressive symptoms of depressed alcoholics.

Adult↗
PubMed1997

Maintenance nortriptyline effects on electroencephalographic sleep in elderly patients with recurrent major depression: double-blind, placebo- and plasma-level-controlled evaluation.

Our aim was to contrast the effects of maintenance nortriptyline and placebo on electroencephalographic sleep measures in elderly recurrent depressives who survived 1-year without recurrence of depression. Patients on nortriptyline took longer to fall asleep and did not maintain sleep better than patients on placebo; however, maintenance nortriptyline was associated with more delta-wave production and higher delta-wave density in the first non-REM (NREM) period relative to the second. Nortriptyline levels were positively but weakly related to all-night delta-wave production during maintenance (accounting for 6.6% of the variance in delta-wave counts). Total phasic REM activity increased 100% under chronic nortriptyline relative to placebo, with a robust increase in the rate of REM activity generation across the night. Effective long-term pharmacotherapy of recurrent major depression is associated with enhancement in the rate of delta-wave production in the first NREM period (i.e., delta sleep ratio) and of REM activity throughout the night.

Aged↗
PubMed1997

Fluoxetine in depressed alcoholics. A double-blind, placebo-controlled trial.

BACKGROUND: The selective serotonergic medication fluoxetine has demonstrated efficacy in the treatment of major depression and has suggested efficacy in the treatment of alcoholism. However, no completed trials with any selective serotonergic medication have been reported in patients who display both major depression and alcoholism, despite previous observations that both depression and alcoholism are associated with low serotonergic functioning. METHODS: Fifty-one patients diagnosed as having comorbid major depressive disorder and alcohol dependence were randomized to receive fluoxetine (n = 25) or placebo (n = 26) in a 12-week, double-blind, parallel-group trial. Weekly ratings of depression and alcohol consumption were obtained throughout the 12-week course of the study. RESULTS: The improvement in depressive symptoms during the medication trial was significantly greater in the fluoxetine group than in the placebo group. Total alcohol consumption during the trial was significantly lower in the fluoxetine group than in the placebo group. CONCLUSIONS: Fluoxetine is effective in reducing the depressive symptoms and the alcohol consumption of patients with comorbid major depressive disorder and alcohol dependence. It is unknown whether these results generalize to the treatment of less depressed and less suicidal alcoholics.

Adult↗
PubMed1997

Neuroendocrine response to 5-hydroxy-L-tryptophan in prepubertal children at high risk of major depressive disorder.

BACKGROUND: Altered serotonergic function has been observed in prepubertal children and adults with an acute episode of major depressive disorder (MDD). However, it is not known whether these alterations are present prior to the onset of MDD. METHODS: A serotonergic precursor, 5-hydroxy-L-tryptophan (L-5HTP) (oxitriptan) (0.8 mg/kg), was administered through an indwelling catheter to 36 children at high risk of MDD (with high family loading for MDD), 31 children with MDD, and 23 low-risk normal controls (with low family loading for mood disorders and no history of psychopathology). Blood samples for cortisol, prolactin (PRL), and growth hormone were obtained every 15 minutes for 180 minutes, beginning 30 minutes before L-5HTP infusion. RESULTS: Children at high risk of MDD and children with MDD had similar hormonal responses following L-5HTP infusion. After controlling for baseline values, both groups secreted significantly less cortisol and more PRL than did the low-risk normal controls, with the PRL finding being limited to girls. There were no between-group differences in baseline cortisol, PRL, or growth hormone secretion measures. CONCLUSIONS: Before the onset of affective illness, high-risk children had the same pattern of neuroendocrine response to the L-5HTP challenge as did children with MDD. These results extend earlier findings of altered serotonergic regulation in association with early-onset depression and indicate that these alterations may represent a trait marker for depression in children.

5-Hydroxytryptophan↗
PubMed1997

Sertraline and norsertraline levels in three breastfed infants.

BACKGROUND: In assessing the safety of medication use in breastfeeding, it is important to know whether the drug used by the mother will be present in the breastfed infant. Compared with data for tricyclic antidepressants (TCAs), which have generally not been found in the plasma of breastfed infants, there are few data on the use of serotonin selective reuptake inhibitors (SSRIs) in breastfeeding. This poses a dilemma for breastfeeding women and their treating clinicians, because of the enhanced tolerability of SSRIs compared with TCAs, and because some patients do not respond well to TCAs. METHOD: Sertraline and norsertraline plasma concentrations were measured in three breastfeeding mother-infant pairs. Maternal and infant plasma samples were drawn a few minutes apart. Two of the infants had an additional sample assayed without contemporaneous maternal samples examined. Drug assay was by high-performance liquid chromatography. Limit of reproducible quantifiability was 2 ng/mL, and limit of detectability was 1 ng/mL. RESULTS: Maternal sertraline dose ranged from 50 to 100 mg/day. All infant plasma samples showed low levels (< 2 ng/mL) of either sertraline and norsertraline or norsertraline alone. Breastfeeding was continued, and the infants have shown no adverse effects on short-term follow-up. CONCLUSION: These data suggest that sertraline and/or its almost inactive metabolite may be present at very low concentrations in the plasma of breastfed infants. No adverse effects were noted in the infants. Limitations of the findings and possible implications for the use of sertraline during breastfeeding are discussed.

1-Naphthylamine↗
PubMed1997

Does lorazepam impair the antidepressant response to nortriptyline and psychotherapy?

BACKGROUND: This analysis sought to determine whether lorazepam influences time to response or rate of response in elderly depressed patients receiving nortriptyline and psychotherapy and to examine clinical and polysomnographic correlates of lorazepam treatment. METHOD: Patients with recurrent major depressive disorder (N = 119; mean +/- SD age = 68.0 +/- 6.1 years; diagnosis defined by Research Diagnostic Criteria) received acute treatment with nortriptyline and interpersonal psychotherapy. Thirty-five patients received open-label adjunctive lorazepam for anxiety or insomnia symptoms (LZ+) and 84 did not. Statistical analyses were conducted between the LZ+ group and a group of 35 patients who received no lorazepam (LZ-) and were matched for anxiety level. Patients had polysomnographic studies prior to treatment and after remission of depressive symptoms. RESULTS: The LZ+ group reported more anxiety on the Brief Symptom Inventory (p = .04) compared with the remaining 84 patients. The LZ+ group had a greater proportion of endogenous depression subtype than the anxiety-matched LZ- group, in addition to more abnormal EEG sleep (higher percentage of REM sleep, shorter REM latency, lower delta sleep ratio). Mean time to initial antidepressant response was no different between groups. However, a significantly greater proportion of LZ+ than LZ- patients responded to acute treatment (91.4% vs. 71.4%; p < .03). CONCLUSION: Adjunctive lorazepam does not slow the antidepressant response to combined antidepressant/psychotherapy treatment in elderly depressed patients, and it is associated with a greater likelihood of antidepressant response. A greater percentage of patients treated with lorazepam have endogenous depression subtype and abnormal sleep findings (EEG) than those who are not treated with lorazepam. Adjunctive lorazepam is useful for treating anxiety in elderly depressed patients.

Age Factors↗
PubMed1997

Double-blind fluoxetine in depressed alcoholic smokers.

Treatment trials involving smoking in alcoholics with major depression are scarce, despite the common co-occurrence of these disorders. In this study, 25 smokers with DSM-III-R diagnoses of both major depressive disorder and alcohol dependence were randomized to fluoxetine or placebo in a 12-week, double-blind, parallel group trial. Almost half (48%) of the patients had made a suicide attempt in the week before hospitalization (where recruitment was performed), and 84 percent reported suicidal ideations during that week. Those in the fluoxetine group demonstrated a significant within-group decrease in smoking during the course of the study, whereas those in the placebo group did not. Those in the fluoxetine group smoked 27 percent fewer cigarettes than those in the placebo group, although this difference was not statistically significant. Cumulative alcohol consumption during the 12 weeks of the pharmacotherapy trial was four times as high in the placebo group as in the fluoxetine group, though this difference was not statistically significant in this limited-sized sample. The change in smoking was significantly associated with a change in drinking. These preliminary findings suggest that fluoxetine has the potential for treating the smoking and drinking behaviors of depressed alcoholic smokers.

Adult↗
PubMed1997

Effects of the postpartum period on nortriptyline pharmacokinetics.

The objective of this research was to investigate sequential serum levels and level/dose ratios of the tricyclic antidepressant nortriptyline (NTP) through the first 17 postpartum weeks. The initial NTP dose was given immediately postpartum to 16 mothers and increased gradually to 70 mg over the first week. A dose of 75 mg was prescribed until adjustment according to serum levels. Serum levels of NTP and its metabolites Z- and E-OH-NTP were determined. At postpartum Week 2, the women developed a mean level/dose (L/D) ratio for NTP of 1.11 (range 0.37 to 3.23), and subsequently experienced an increase in the L/D ratios which continued through Week 6. At Week 8, the NTP L/D ratios declined, and became relatively stable at Week 11 and beyond. For postpartum women treated with NTP, side effect profiles should be carefully followed during the first 6 weeks after delivery as a clinical marker for elevation of serum levels. Since our highest L/D ratios for NTP occurred at Week 6, a serum level is recommended at this time. If the dose needs to be lowered to maintain a nontoxic level, a repeat serum level should be obtained at Week 11, at which time an increase in dose may be required.

Adult↗
PubMed1997

Nortriptyline and its hydroxymetabolites in breastfeeding mothers and newborns.

We previously reported the serum nortriptyline levels of a series of breastfeeding mother-infant pairs. Nortriptyline was below the level of detectability in the infants' sera; however, two young infants aged 10 weeks or less had low concentrations of 10-hydroxy-nortriptyline. Because very young breastfeeding infants are likely to be at increased risk for toxicity, we have focused our study on breastfeeding newborns. We present additional data from six mothers and their infants (4 weeks of age), as well as data from one prematurely born baby. We were able to quantify nortriptyline in one infant and another had higher levels of hydroxymetabolites than previously reported, although still very low. No adverse clinical effects were observed in the infants.

Breast Feeding↗