Paul Goodnick - Academia.edu (original) (raw)
Papers by Paul Goodnick
Expert Opin Pharmacother, 2007
Seligiline, a monoamine oxidase inhibitor, has been previously approved by the US FDA for adjunct... more Seligiline, a monoamine oxidase inhibitor, has been previously approved by the US FDA for adjunctive treatment of Parkinson's disease. At present, it has been found to be effective in a transdermal system when administered daily in the treatment of major depressive disorder. The minimum dosage of 6 mg/24 h was effective in two trials; this dosage did not require any dietary precautions. Higher doses of 9 mg/24 h and 12 mg/24 h may also not require restrictions, however, current data is insufficient. Furthermore, a randomized 52-week prevention study found significant benefits for continuance of this treatment. There are several types of safety data available. First, there have been no reports of hypertensive crisis in any patient receiving selegiline via this transdermal system at any of the three doses. Tyramine challenge studies have found a comfortable cushion of safety at selegiline doses of 6 mg/24 h. Other side effects include a slightly higher rate of orthostatic hypotension, insomnia and, most frequently, application site reactions. There are no significant effects on weight or sexual side effects. In terms of drug interactions, carbamazepine was found to significantly increase seligiline levels (however, carbamazepine should be contraindicated). Direct sympathomimetics may be safe, but indirect ones are thought to put the patient at risk. Finally, due to risk of serotonin syndrome, other medications contraindicated include: selective serotonin re-uptake inhibitors, serotonin-noradrenaline re-uptake inhibitors and multiple analgesics - in particular meperidine. To prevent toxic drug interactions at initiation of seligiline transdermal system therapy, all mediactions that are at risk should be completely stopped a minimum of 4-5 times their respective half-lifes for full elimination. This is generally a time period of 1 week. Upon stopping treatment with selegiline, 2 weeks should pass prior to beginning any medication at risk for drug interactions.
ABSTRACT An 8-week open, non-randomized study compared the dopamine-specific antidepressant, bupr... more ABSTRACT An 8-week open, non-randomized study compared the dopamine-specific antidepressant, bupropion, to the serotonin-specific antidepressant, fluoxetine. Of the 57 patients, 10 met DSM-IIIR criteria for bipolar depression. The other 47 met DSM-IIIR criteria for major depressive disorder. Of these, 23 were subclassified as “atypical” whereas 24 were “typical” based on sleep and appetite patterns. In bipolar patients, depression (as indicated by fall in Beck Depression Inventory [BDI] score) improved significantly in eight of nine patients following administration of bupropion (the mean fall = 16.3 [p < 0.003]). In atypical depression patients, depression as measured by BDI improved significantly after bupropion, but not after fluoxetine. Significant improvement was seen following bupropion in 9 of 14, but only in 2 of 9 following fluoxetine. In typical depression, BDI dropped 6.0 (p = 0.09) after bupropion, and 11.8 (p = 0.002) after fluoxetine. Significant improvement was seen after bupropion in 2 or 11, but after fluoxetine in 7 of 13 (V2 = 3.10, p = 0.07). Larger numbers in controlled studies are needed for replication, but there may yet be a role for biochemical specificity of treatment of depression, with bupropion an effective antidepressant drug in bipolar and atypical depressed patients and with fluoxetine effective in typical depression.
American Journal of Psychiatry, Oct 7, 2014
TO THE EDITOR: The sexual side effects of selective serotonin reuptake inhibitors (SSRIs) may adv... more TO THE EDITOR: The sexual side effects of selective serotonin reuptake inhibitors (SSRIs) may adversely affect compliance. Loss of libido, anorgasmia, and delayed ejaculation in males seem to occur far more frequently than is indicated in package inserts and may affect as many as two-thirds of patients (1). Although SSRIs may differ in propensity to cause sexual dysfunction, this has not been studied in comparative controlled trials. We report two cases in which the highly selective serotonin reuptake inhibitor citalopram did not cause sexual impairment in patients who had experienced such events with other SSRIs.
Ann Clin Psychiatry, 1991
ABSTRACT Patients meeting DSM-III-R criteria for major depressive disorder were begun on bupropio... more ABSTRACT Patients meeting DSM-III-R criteria for major depressive disorder were begun on bupropion with increases to a maximum of 450 mg/day. Fifteen of 23 patients in the acute study had at least a 50% fall in the Beck Depression Inventory (BDI) after a mean of 4.6 weeks (27% within 2 weeks). Thirteen (57%) had side effects, but none involved major adverse events, requiring discontinuation or reduction in dose. Onset of side effects preceeded clinical response (p = 0.05). Side effects were not related to dose or blood level. Long-term follow-up of 25 patients who responded for 12.0 ± 5.7 months was associated with a plateau at 2 months, with duration of side effects of 2.2 ± 2.8 months, and with relapse in only one patient (4%), who developed a blood level of 107 ng/mL and regained remission on reduction of dosage. Thus, bupropion is an effective acute and long-term treatment for depression with stabilization after 2 months, and with few side effects that may occur prior to clinical response but resolve quickly during treatment.
Ann Clin Psychiatry, 1989
ABSTRACT In a series of 39 patients with major depression, 16 were found to have delta thyroid-st... more ABSTRACT In a series of 39 patients with major depression, 16 were found to have delta thyroid-stimulating hormone (TSH) results greater than 20, suggestive of subclinical hypothyroidism. The two groups of patients did not differ in severity of depression (Beck Depression Inventory), in subclinical symptoms of mood disorder (the General Behavior Inventory), in family history of depression, or in family history of thyroid disorder. Thyroid hormone treatment alone was given to 8 of these 16, all of whom had full remissions (p = 0.004). Six-month follow-up data indicated that these remissions were maintained, while thyroid function measures were significantly improved. Depressed patients who have thyroid insufficiency as determined by delta TSH results may respond to treatment with thyroid hormone, without need for antidepressants.
J Clin Psychopharmacol, 1982
Clin Pharmacol Ther, 1981
The elimination half-life (t1/2E) of lithium carbonate in red blood cells, plasma, and urine was ... more The elimination half-life (t1/2E) of lithium carbonate in red blood cells, plasma, and urine was measured in 30 patients hospitalized for primary affective disorder. Duration of Li treatment at time of sampling was found to have a direct effect on lengthening time course. Patients on their initial course of Li had the lowest t1/2s: 1.12 (urine), 1.28 (plasma), and 1.22 days (red blood cells); those less than 1 Vr on Li had intermediate values: 1.85, 1.65, and 1.75 days; and those more than I continous year on Li had the longest mean t1/2s: 2.40, 2.43, and 2.24 days. These results for urine (p < 0.01) and plasma (p < 0.05) are further evidence that Li may stimulate the production of an endogenous regulator of Li efflux. This regulator may prove to be an important factor in planning of long-term Li prophylaxis.
Expert Opin Pharmacother, 2001
Rapid cycling bipolar disorder (RCBD) is defined in the fourth edition of the Diagnostic and Stat... more Rapid cycling bipolar disorder (RCBD) is defined in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a type of manic-depressive illness in which the patient experiences four or more episodes of mania and/or major depression per year. It was first reported as a consequence of the reduced effectiveness of lithium carbonate in the treatment and prophylaxis of this form of bipolar disorder (BD) in contrast to those with less frequent cycling. Among the anticonvulsants, there have been reports with different degrees of controlled data concerning carbamazepine, valproate, lamotrigine, topiramate, gabapentin and primidone. There is a paucity of double-blind studies, but what is available supports the use of lamotrigine. There is open data supporting the use of carbamazepine, valproate and topiramate. Regarding other classes, nimodipine may have specific utility in ultradian- (ultra-ultra-) or ultra-RCBD and there is double-blind data regarding the specific utility of olanzapine in RCBD. Low thyroid function may be a factor in development of RCBD; therapies aimed at elevating thyroid levels, even beyond the usual range, have frequently produced benefits in open trials. More research is needed into the possible therapeutic benefits of verapamil, bupropion, choline, light therapy and electroconvulsive therapy (ECT).
Journal of Chronic Fatigue Syndrome, 2007
Centers for Disease Control criteria for chronic fatigue syndrome (CFS) specifically recognize th... more Centers for Disease Control criteria for chronic fatigue syndrome (CFS) specifically recognize that patients can have both CFS and depression. The clinician's challenge is to judge for each individual patient whether the complaint of fatigue is primarily depression, physical illness, such as CFS, or a combination of both.
Expert Opin Pharmacother, 2002
Hyperprolactinaemia has been associated with a variety of side effects including amenorrhoea, gal... more Hyperprolactinaemia has been associated with a variety of side effects including amenorrhoea, galactorrhoea, sexual dysfunction, breast engorgement and osteoporosis. Since the mid-1970s, the impact of antipsychotics on human prolactin (hPrl) levels has been investigated. Baseline levels of hPrl were found to be similar in healthy controls and patients who were diagnosed as having schizophrenia. Short-term acute studies done after single parenteral or oral doses of phenothiazines found rapid two- to tenfold increases in hPrl. Similar increases were found in longer term studies that reported increases of three times in both men and women after 3 days that doubled again after several weeks of treatment. A study of longer term injectable fluphenazine enanthate found that elevation induced by a single injection lasted up to 28 days. The same results with significant increases have been reported with the butyrophenone, haloperidol. Substantial increases are found after single injections (up to nine times) and after weeks of treatment (up to three times sustained). Thus, early literature believed that there might be an association between these induced changes and response to therapy. However, prolactin is secreted by the anterior pituitary and is under inhibitory control of dopamine released from the tuberoinfundibular neurones. Thus, increases in prolactin are due to antipsychotic impact on tuberoinfundibular tract, one of four dopamine-related tracts. With the application of clozapine and other atypical antipsychotics, it was found that medications can successfully treat psychosis without increasing hPrl. In fact, early single-dose trails found clozapine to reduce hPrl by 16%. Later studies replicated this result and also found that up to 6 weeks of administration led to reductions in hPrl of up to 80%. Risperidone, however, has been found to persistently elevate hPrl in studies, despite its impact on other receptor sites. Olanzapine, quetiapine and ziprasidone have all been found to have little effect or produce decreases in hPrl. Most recently, aripiprazole, in early studies, appears to produce significant reductions in hPrl while maintaining therapeutic efficacy for psychosis.
Clin Neuropharmacol, 1984
Expert Opin Pharmacother, 2002
The QT interval measuring depolarisation and repolarisation has, when lengthened, been implicated... more The QT interval measuring depolarisation and repolarisation has, when lengthened, been implicated as a risk factor for the development of torsades de pointes and sudden death, particularly in patients predisposed to these complications due to cardiovascular impairment. Since some of the medications used in psychiatry have been implicated, an extensive review of available literature was made of the major classes, including antipsychotics, antidepressants, lithium, anticonvulsants and benzodiazepines. Further, where no publications were found on a particular medication, the pharmaceutical firms responsible for these items were contacted concerning possibly unpublished data. Results of the survey indicate that there may be difficulty in one of three situations: immediate (in the first minutes to hours after oral or parenteral administration), short-term use of 4 -12 weeks or long-term use of ≥ 6 months. Based on this approach, the greatest concern is directed at the immediate application of haloperidol, droperidol, pimozide and trazodone, the short-term use of thioridazine, pimozide, sertindole, nortriptyline, clomipramine, doxepin and the long-term use of clozapine, olanzapine and carbamazepine. It is of interest that a reduction in QTc is reported with aripiprazole. Among the antidepressants, the tertiary tricyclic antidepressants (imipramine, amitriptyline and doxepin) appear to have a more general impact, while the secondary tricyclic antidepressants (nortriptyline, desipramine) may impact more on children and the elderly. Among other antidepressants, the only reports of torsades de pointes appeared to occur with mirtazapine. It was also of interest to find data showing no effect or reductions in QTc produced by sertraline, citalopram, paroxetine and bupropion in multiple studies. Effects of medications on other heart parameters are also briefly reviewed. In particular, the safety of sertraline in post-MI patients and of bupropion in heart disease patients is highlighted. Little information was available on other classes of medications used in psychiatric disorders. What is available concerning lithium, the anticonvulsants and the benzodiazepines indicates little effect on the QTc, although there may be effects on other cardiovascular parameters.
Biol Psychiat, 2000
Background: A previous retrospective study revealed that a high pretreatment platelet serotonin (... more Background: A previous retrospective study revealed that a high pretreatment platelet serotonin (5-HT) concentration was associated with a low response to serotonergic antidepressants in drug-free major depressives. We have examined such a relationship in depressive patients treated with paroxetine. Methods: Seventy-four drug-free major depressives (DSM-IV) were admitted to the study. Clinical ratings were performed and blood was drawn prior to the initiation of treatment and after 4 weeks of paroxetine (20 mg/day). The concentrations of 5-HT, 5-hydroxyindoleacetic acid, and tryptophan were determined in plasma and blood. Results: Paroxetine treatment reduced platelet 5-HT to 17% of baseline after 4 weeks of treatment. Responder patients had a pretreatment platelet 5-HT concentration 22% lower than nonresponders (p Ͻ .035). Admission HAMD scores, plasma paroxetine concentration, or platelet 5-HT concentration at endpoint did not differ between responders and nonresponders. Yet, the response rate was 11% in patients with high pretreatment platelet 5-HT (Ͼ 900 ng/10 9 platelets) and 50% in those below that value (p Ͻ .004). Conclusions: These findings support that depressed patients with a high pretreatment platelet 5-HT concentration have a poor therapeutic outcome after treatment with a standard paroxetine dose. These differences may be related to the existence of molecular differences in the 5-HT transporter.
Centers for Disease Control criteria for chronic fatigue syndrome (CFS) specifically recognize th... more Centers for Disease Control criteria for chronic fatigue syndrome (CFS) specifically recognize that patients can have both CFS and depression. The clinician's challenge is to judge for each individual patient whether the complaint of fatigue is primarily depression, physical illness, such as CFS, or a combination of both.
The Psychiatric Clinics of North America, Jul 1, 2003
Conflicting or sparse data on predictors of treatment response in depression have resulted in lac... more Conflicting or sparse data on predictors of treatment response in depression have resulted in lack of clear guidelines in choosing antidepressant treatment. Critical to treatment outcome are accurate diagnosis and adequate treatment. Other data easy to obtain, such as age, gender, and marital status, have failed to be consistent predictors; more elaborate studies, such as receptor analysis or neuroimaging, are not yet accessible to most clinicians or economically feasible; however, they offer hope for the future, when more biologically based diagnostic distinctions may come to guide treatment choices.
the response rate was 11% in patients with high pretreatment platelet 5-HT concentration (Ͼ900 ng... more the response rate was 11% in patients with high pretreatment platelet 5-HT concentration (Ͼ900 ng/10 9 platelets) and 50% in those below that value (p Ͻ .004)."
Expert Opin Pharmacother, 2007
Seligiline, a monoamine oxidase inhibitor, has been previously approved by the US FDA for adjunct... more Seligiline, a monoamine oxidase inhibitor, has been previously approved by the US FDA for adjunctive treatment of Parkinson&amp;amp;amp;#39;s disease. At present, it has been found to be effective in a transdermal system when administered daily in the treatment of major depressive disorder. The minimum dosage of 6 mg/24 h was effective in two trials; this dosage did not require any dietary precautions. Higher doses of 9 mg/24 h and 12 mg/24 h may also not require restrictions, however, current data is insufficient. Furthermore, a randomized 52-week prevention study found significant benefits for continuance of this treatment. There are several types of safety data available. First, there have been no reports of hypertensive crisis in any patient receiving selegiline via this transdermal system at any of the three doses. Tyramine challenge studies have found a comfortable cushion of safety at selegiline doses of 6 mg/24 h. Other side effects include a slightly higher rate of orthostatic hypotension, insomnia and, most frequently, application site reactions. There are no significant effects on weight or sexual side effects. In terms of drug interactions, carbamazepine was found to significantly increase seligiline levels (however, carbamazepine should be contraindicated). Direct sympathomimetics may be safe, but indirect ones are thought to put the patient at risk. Finally, due to risk of serotonin syndrome, other medications contraindicated include: selective serotonin re-uptake inhibitors, serotonin-noradrenaline re-uptake inhibitors and multiple analgesics - in particular meperidine. To prevent toxic drug interactions at initiation of seligiline transdermal system therapy, all mediactions that are at risk should be completely stopped a minimum of 4-5 times their respective half-lifes for full elimination. This is generally a time period of 1 week. Upon stopping treatment with selegiline, 2 weeks should pass prior to beginning any medication at risk for drug interactions.
ABSTRACT An 8-week open, non-randomized study compared the dopamine-specific antidepressant, bupr... more ABSTRACT An 8-week open, non-randomized study compared the dopamine-specific antidepressant, bupropion, to the serotonin-specific antidepressant, fluoxetine. Of the 57 patients, 10 met DSM-IIIR criteria for bipolar depression. The other 47 met DSM-IIIR criteria for major depressive disorder. Of these, 23 were subclassified as “atypical” whereas 24 were “typical” based on sleep and appetite patterns. In bipolar patients, depression (as indicated by fall in Beck Depression Inventory [BDI] score) improved significantly in eight of nine patients following administration of bupropion (the mean fall = 16.3 [p < 0.003]). In atypical depression patients, depression as measured by BDI improved significantly after bupropion, but not after fluoxetine. Significant improvement was seen following bupropion in 9 of 14, but only in 2 of 9 following fluoxetine. In typical depression, BDI dropped 6.0 (p = 0.09) after bupropion, and 11.8 (p = 0.002) after fluoxetine. Significant improvement was seen after bupropion in 2 or 11, but after fluoxetine in 7 of 13 (V2 = 3.10, p = 0.07). Larger numbers in controlled studies are needed for replication, but there may yet be a role for biochemical specificity of treatment of depression, with bupropion an effective antidepressant drug in bipolar and atypical depressed patients and with fluoxetine effective in typical depression.
American Journal of Psychiatry, Oct 7, 2014
TO THE EDITOR: The sexual side effects of selective serotonin reuptake inhibitors (SSRIs) may adv... more TO THE EDITOR: The sexual side effects of selective serotonin reuptake inhibitors (SSRIs) may adversely affect compliance. Loss of libido, anorgasmia, and delayed ejaculation in males seem to occur far more frequently than is indicated in package inserts and may affect as many as two-thirds of patients (1). Although SSRIs may differ in propensity to cause sexual dysfunction, this has not been studied in comparative controlled trials. We report two cases in which the highly selective serotonin reuptake inhibitor citalopram did not cause sexual impairment in patients who had experienced such events with other SSRIs.
Ann Clin Psychiatry, 1991
ABSTRACT Patients meeting DSM-III-R criteria for major depressive disorder were begun on bupropio... more ABSTRACT Patients meeting DSM-III-R criteria for major depressive disorder were begun on bupropion with increases to a maximum of 450 mg/day. Fifteen of 23 patients in the acute study had at least a 50% fall in the Beck Depression Inventory (BDI) after a mean of 4.6 weeks (27% within 2 weeks). Thirteen (57%) had side effects, but none involved major adverse events, requiring discontinuation or reduction in dose. Onset of side effects preceeded clinical response (p = 0.05). Side effects were not related to dose or blood level. Long-term follow-up of 25 patients who responded for 12.0 ± 5.7 months was associated with a plateau at 2 months, with duration of side effects of 2.2 ± 2.8 months, and with relapse in only one patient (4%), who developed a blood level of 107 ng/mL and regained remission on reduction of dosage. Thus, bupropion is an effective acute and long-term treatment for depression with stabilization after 2 months, and with few side effects that may occur prior to clinical response but resolve quickly during treatment.
Ann Clin Psychiatry, 1989
ABSTRACT In a series of 39 patients with major depression, 16 were found to have delta thyroid-st... more ABSTRACT In a series of 39 patients with major depression, 16 were found to have delta thyroid-stimulating hormone (TSH) results greater than 20, suggestive of subclinical hypothyroidism. The two groups of patients did not differ in severity of depression (Beck Depression Inventory), in subclinical symptoms of mood disorder (the General Behavior Inventory), in family history of depression, or in family history of thyroid disorder. Thyroid hormone treatment alone was given to 8 of these 16, all of whom had full remissions (p = 0.004). Six-month follow-up data indicated that these remissions were maintained, while thyroid function measures were significantly improved. Depressed patients who have thyroid insufficiency as determined by delta TSH results may respond to treatment with thyroid hormone, without need for antidepressants.
J Clin Psychopharmacol, 1982
Clin Pharmacol Ther, 1981
The elimination half-life (t1/2E) of lithium carbonate in red blood cells, plasma, and urine was ... more The elimination half-life (t1/2E) of lithium carbonate in red blood cells, plasma, and urine was measured in 30 patients hospitalized for primary affective disorder. Duration of Li treatment at time of sampling was found to have a direct effect on lengthening time course. Patients on their initial course of Li had the lowest t1/2s: 1.12 (urine), 1.28 (plasma), and 1.22 days (red blood cells); those less than 1 Vr on Li had intermediate values: 1.85, 1.65, and 1.75 days; and those more than I continous year on Li had the longest mean t1/2s: 2.40, 2.43, and 2.24 days. These results for urine (p < 0.01) and plasma (p < 0.05) are further evidence that Li may stimulate the production of an endogenous regulator of Li efflux. This regulator may prove to be an important factor in planning of long-term Li prophylaxis.
Expert Opin Pharmacother, 2001
Rapid cycling bipolar disorder (RCBD) is defined in the fourth edition of the Diagnostic and Stat... more Rapid cycling bipolar disorder (RCBD) is defined in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a type of manic-depressive illness in which the patient experiences four or more episodes of mania and/or major depression per year. It was first reported as a consequence of the reduced effectiveness of lithium carbonate in the treatment and prophylaxis of this form of bipolar disorder (BD) in contrast to those with less frequent cycling. Among the anticonvulsants, there have been reports with different degrees of controlled data concerning carbamazepine, valproate, lamotrigine, topiramate, gabapentin and primidone. There is a paucity of double-blind studies, but what is available supports the use of lamotrigine. There is open data supporting the use of carbamazepine, valproate and topiramate. Regarding other classes, nimodipine may have specific utility in ultradian- (ultra-ultra-) or ultra-RCBD and there is double-blind data regarding the specific utility of olanzapine in RCBD. Low thyroid function may be a factor in development of RCBD; therapies aimed at elevating thyroid levels, even beyond the usual range, have frequently produced benefits in open trials. More research is needed into the possible therapeutic benefits of verapamil, bupropion, choline, light therapy and electroconvulsive therapy (ECT).
Journal of Chronic Fatigue Syndrome, 2007
Centers for Disease Control criteria for chronic fatigue syndrome (CFS) specifically recognize th... more Centers for Disease Control criteria for chronic fatigue syndrome (CFS) specifically recognize that patients can have both CFS and depression. The clinician's challenge is to judge for each individual patient whether the complaint of fatigue is primarily depression, physical illness, such as CFS, or a combination of both.
Expert Opin Pharmacother, 2002
Hyperprolactinaemia has been associated with a variety of side effects including amenorrhoea, gal... more Hyperprolactinaemia has been associated with a variety of side effects including amenorrhoea, galactorrhoea, sexual dysfunction, breast engorgement and osteoporosis. Since the mid-1970s, the impact of antipsychotics on human prolactin (hPrl) levels has been investigated. Baseline levels of hPrl were found to be similar in healthy controls and patients who were diagnosed as having schizophrenia. Short-term acute studies done after single parenteral or oral doses of phenothiazines found rapid two- to tenfold increases in hPrl. Similar increases were found in longer term studies that reported increases of three times in both men and women after 3 days that doubled again after several weeks of treatment. A study of longer term injectable fluphenazine enanthate found that elevation induced by a single injection lasted up to 28 days. The same results with significant increases have been reported with the butyrophenone, haloperidol. Substantial increases are found after single injections (up to nine times) and after weeks of treatment (up to three times sustained). Thus, early literature believed that there might be an association between these induced changes and response to therapy. However, prolactin is secreted by the anterior pituitary and is under inhibitory control of dopamine released from the tuberoinfundibular neurones. Thus, increases in prolactin are due to antipsychotic impact on tuberoinfundibular tract, one of four dopamine-related tracts. With the application of clozapine and other atypical antipsychotics, it was found that medications can successfully treat psychosis without increasing hPrl. In fact, early single-dose trails found clozapine to reduce hPrl by 16%. Later studies replicated this result and also found that up to 6 weeks of administration led to reductions in hPrl of up to 80%. Risperidone, however, has been found to persistently elevate hPrl in studies, despite its impact on other receptor sites. Olanzapine, quetiapine and ziprasidone have all been found to have little effect or produce decreases in hPrl. Most recently, aripiprazole, in early studies, appears to produce significant reductions in hPrl while maintaining therapeutic efficacy for psychosis.
Clin Neuropharmacol, 1984
Expert Opin Pharmacother, 2002
The QT interval measuring depolarisation and repolarisation has, when lengthened, been implicated... more The QT interval measuring depolarisation and repolarisation has, when lengthened, been implicated as a risk factor for the development of torsades de pointes and sudden death, particularly in patients predisposed to these complications due to cardiovascular impairment. Since some of the medications used in psychiatry have been implicated, an extensive review of available literature was made of the major classes, including antipsychotics, antidepressants, lithium, anticonvulsants and benzodiazepines. Further, where no publications were found on a particular medication, the pharmaceutical firms responsible for these items were contacted concerning possibly unpublished data. Results of the survey indicate that there may be difficulty in one of three situations: immediate (in the first minutes to hours after oral or parenteral administration), short-term use of 4 -12 weeks or long-term use of ≥ 6 months. Based on this approach, the greatest concern is directed at the immediate application of haloperidol, droperidol, pimozide and trazodone, the short-term use of thioridazine, pimozide, sertindole, nortriptyline, clomipramine, doxepin and the long-term use of clozapine, olanzapine and carbamazepine. It is of interest that a reduction in QTc is reported with aripiprazole. Among the antidepressants, the tertiary tricyclic antidepressants (imipramine, amitriptyline and doxepin) appear to have a more general impact, while the secondary tricyclic antidepressants (nortriptyline, desipramine) may impact more on children and the elderly. Among other antidepressants, the only reports of torsades de pointes appeared to occur with mirtazapine. It was also of interest to find data showing no effect or reductions in QTc produced by sertraline, citalopram, paroxetine and bupropion in multiple studies. Effects of medications on other heart parameters are also briefly reviewed. In particular, the safety of sertraline in post-MI patients and of bupropion in heart disease patients is highlighted. Little information was available on other classes of medications used in psychiatric disorders. What is available concerning lithium, the anticonvulsants and the benzodiazepines indicates little effect on the QTc, although there may be effects on other cardiovascular parameters.
Biol Psychiat, 2000
Background: A previous retrospective study revealed that a high pretreatment platelet serotonin (... more Background: A previous retrospective study revealed that a high pretreatment platelet serotonin (5-HT) concentration was associated with a low response to serotonergic antidepressants in drug-free major depressives. We have examined such a relationship in depressive patients treated with paroxetine. Methods: Seventy-four drug-free major depressives (DSM-IV) were admitted to the study. Clinical ratings were performed and blood was drawn prior to the initiation of treatment and after 4 weeks of paroxetine (20 mg/day). The concentrations of 5-HT, 5-hydroxyindoleacetic acid, and tryptophan were determined in plasma and blood. Results: Paroxetine treatment reduced platelet 5-HT to 17% of baseline after 4 weeks of treatment. Responder patients had a pretreatment platelet 5-HT concentration 22% lower than nonresponders (p Ͻ .035). Admission HAMD scores, plasma paroxetine concentration, or platelet 5-HT concentration at endpoint did not differ between responders and nonresponders. Yet, the response rate was 11% in patients with high pretreatment platelet 5-HT (Ͼ 900 ng/10 9 platelets) and 50% in those below that value (p Ͻ .004). Conclusions: These findings support that depressed patients with a high pretreatment platelet 5-HT concentration have a poor therapeutic outcome after treatment with a standard paroxetine dose. These differences may be related to the existence of molecular differences in the 5-HT transporter.
Centers for Disease Control criteria for chronic fatigue syndrome (CFS) specifically recognize th... more Centers for Disease Control criteria for chronic fatigue syndrome (CFS) specifically recognize that patients can have both CFS and depression. The clinician's challenge is to judge for each individual patient whether the complaint of fatigue is primarily depression, physical illness, such as CFS, or a combination of both.
The Psychiatric Clinics of North America, Jul 1, 2003
Conflicting or sparse data on predictors of treatment response in depression have resulted in lac... more Conflicting or sparse data on predictors of treatment response in depression have resulted in lack of clear guidelines in choosing antidepressant treatment. Critical to treatment outcome are accurate diagnosis and adequate treatment. Other data easy to obtain, such as age, gender, and marital status, have failed to be consistent predictors; more elaborate studies, such as receptor analysis or neuroimaging, are not yet accessible to most clinicians or economically feasible; however, they offer hope for the future, when more biologically based diagnostic distinctions may come to guide treatment choices.
the response rate was 11% in patients with high pretreatment platelet 5-HT concentration (Ͼ900 ng... more the response rate was 11% in patients with high pretreatment platelet 5-HT concentration (Ͼ900 ng/10 9 platelets) and 50% in those below that value (p Ͻ .004)."