Pharmacotherapy of Depression: The Acute and Long-Term Perspective
Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen in Handbook of Depression and Anxiety, 2003
Kocsis and colleagues [26] studied the use of desipramine to treat chronic depression. Their study had three phases: an acute open treatment with desipramine (10 weeks), an open continuation phase (16 weeks), and a randomized placebo-controlled treatment with desipramine for up to 2 years. Only patients successfully treated in the first phase continued on to the open treatment with desipramine. In the acute treatment phase, 41% of patients were full responders and 22% were partial responders. Sixty patients who were either full or partial “remitters” continued onto the next phase. In the continuation phase, the majority of patients (83%) maintained their response status: 7 partial remitters became full remitters; 3 full remitters became partial remitters; and 1 partial remitter relapsed. In the maintenance phase, patients receiving a placebo were four times more likely than the treatment group to have a recurrence of major depression.
Anxiolytics: Predicting Response/Maximizing Efficacy
Mark S. Gold, R. Bruce Lydiard, John S. Carman in Advances in Psychopharmacology: Predicting and Improving Treatment Response, 2018
Panic attacks stop after about 3 weeks of adequate doses of a tricyclic or a monoamine oxidase inhibitor. Tricyclics are safer than MAOIs and do not require a careful diet. Specifically, desipramine is very effective and among tricyclics has a minimum of anticholinergic and antihistamine side effects. Any of these drugs, including desipramine, is associated with peripheral hypersympathetic side effects for the first few weeks of treatment before tolerance develops to them. This early period can be associated with increased panic attacks, and patients usually perceive themselves to be worse in these weeks. Often they flee medication for these reasons. Also, they feel that they are being controlled by a drug that they sense by these side effects. In their compulsive personality structure, they stubbornly insist to control themselves. This is another major source of medication noncompliance. Patients who refuse medication don’t get better. Compliance with treatment can be assured by (1) warning the patient in advance about side effects and how she is likely to feel about them, (2) emphasizing that they are temporary, (3) not increasing desipramine precipitously, (4) using two drugs in combination, and (5) measurement of drug levels to assure the patient is taking the drug (s) and the level is appropriate.
Overview of Agents with Efficacy in Binge Eating
Susan L. McElroy, David B. Allison, George A. Bray in Obesity and Mental Disorders, 2006
Initial studies were conducted before the publication of the provisional DSM-IV criteria for BED and employed tricyclic antidepressants in clinical conditions closely related to this diagnosis (17,18). In a first double-blind placebo-controlled study, McCaan et al. (17) noted that desipramine was significantly superior to placebo in reducing binge eating in 23 patients with non-purging BN. At the end of the trial, 60% of desipramine treated patients did not binge eat, compared with 15% of placebo-treated women. Additionally, patients quickly relapsed after the discontinuation of the medication. However, there were no differences between desipramine and placebo in change in weight, BMI, perception of body image, or depressive symptoms. These results lead to the hypothesis that antidepressants might also work in eating disorders by suppressing appetite rather than elevating mood, and that desipramine might also have a therapeutic effect in patients with BED. A second trial conducted by Alger et al. (18) compared imipramine 150–200 mg/ day with placebo in obese binge eaters (individuals with a binge eating scale score –27) and normal weight BN patients. This study included an additional naltrexone group. A median reduction in binge eating frequency greater than 90% was observed, but there was no statistically significant difference between drug and placebo (due to an extremely high placebo response rate of 70%). This high placebo response along with the small sample size makes these results difficult to interpret. Adverse reactions for imipramine included drug rash and elevated liver enzymes; for naltrexone they included headache, nausea, agitation, diaphoresis, and elevated liver enzymes.
Antidepressants with different mechanisms of action show different chronopharmacological profiles in the tail suspension test in mice
Published in Chronobiology International, 2019
Hiroshi Kawai, Reiko Iwadate, Takuya Ishibashi, Naomi Kudo, Yoichi Kawashima, Atsushi Mitsumoto
To analyze the possibility that the difference in tissue drug levels among different ZTs causes the chronopharmacological activity observed in TST, we analyzed the plasma and brain drug levels after administration using the same treatment schedule for TST. As the dosing time-dependent difference in antidepressant activity was large between ZT1 and ZT13 in all four tested drugs (Figure 2), tissue drug levels were analyzed at these ZTs. Desipramine, an imipramine metabolite, has antidepressant activity and has comparable potency as that of imipramine itself (Tatsumi et al. 1997). Therefore, desipramine levels were also measured in imipramine-treated mice. The results are shown in Figures 6 and 7. The differences between ZT1 and ZT13 were small and not significant in all four drugs.
Pharmacological interventions for anxiety in Parkinson’s disease sufferers
Published in Expert Opinion on Pharmacotherapy, 2018
Hideyuki Sawada, Atsushi Umemura, Masayuki Kohsaka, Satoshi Tomita, Kwiyoung Park, Tomoko Oeda, Kenji Yamamoto
Devos et al. conducted a placebo-controlled randomized clinical trial of the tricyclic antidepressant desipramine (75 mg/day) and the SSRI citalopram (20 mg/day) against depression in PD [28]. Depression and anxiety were assessed using the Montgomery Asberg Depression Rating Scale (MADRS) as the primary outcome measure and the overall Hamilton Anxiety Rating Scale as a secondary outcome measure, respectively. Depression and anxiety were scored at baseline and 14 and 30 days after baseline. Compared with placebo, MADRS scores significantly improved with desipramine or citalopram at 30 days; however, only desipramine was significantly effective at 14 days, suggesting that desipramine works earlier against depression than citalopram. Anxiety scores were improved by placebo, desipramine, and citalopram at 14 days, with no significant difference among the three groups. At 30 days, Hamilton Anxiety Scale scores for desipramine and citalopram groups were significantly better than for the placebo group, but the effect size was modest. This study demonstrated that desipramine is an effective treatment for depression earlier than citalopram, and that anxiety can be improved by either desipramine or citalopram. The effect size against anxiety seems very modest.
Neuroprotective benefits of grape seed and skin extract in a mouse model of Parkinson’s disease
Published in Nutritional Neuroscience, 2021
Sarah Ben Youssef, Guillaume Brisson, Hélène Doucet-Beaupré, Anne-Marie Castonguay, Charles Gora, Mohamed Amri, Martin Lévesque
The intrastriatal stereotaxic unilateral injection of 6-OHDA was used to establish a model of PD (Stott et al., 2014). The mice received a special diet consisting of peanut butter, mashed pellets and DietGel® Boost (ClearH2O, Westbrook, ME) 3 days prior to surgery to help them cope with postsurgical weight loss. Desipramine (2.5 mg/mL; Sigma) was administered ip at a dose of 10 mL/kg body weight 15 min prior to the animal being anesthetized to increase the selectivity and efficacy of the 6-OHDA-induced lesions (Thiele et al., 2012). The animals were anesthetized with 4% isoflurane and immobilized in a stereotaxic apparatus (Stoelting, Wood Dale, IL). Lesions were made by the unilateral injection of 6-OHDA (4.5 μg total dose, 1.5 μL/site) into the right striatum at the following coordinates: AP: +0.8 mm; ML: +1.6 mm; DV: −2.4 mm (DV, taken from the surface of the brain) from bregma (Bradley et al., 2007). The sham-operated animals received an injection of vehicle only (0.2% ascorbate in 0.9% sodium chloride) at the same coordinates. The 6-OHDA solution was prepared fresh, protected from light to avoid auto-oxidation and administered at a rate of 0.5 μL/min using a 5 μL microinjector. The syringe was left in place for 5 min after 6-OHDA delivery before slowly retracting it to allow for toxin diffusion and prevent toxin reflux. The mice were then sutured and provided with postsurgical care with daily subcutaneous injections of saline (0.9% NaCl) and free access to the special diet described above to avoid drastic postsurgery weight loss.
Related Knowledge Centers
- Anticholinergic
- Antidepressant
- Norepinephrine Reuptake Inhibitor
- Selective Serotonin Reuptake Inhibitor
- Tricyclic Antidepressant
- Depression
- Serotonin Reuptake Inhibitor
- Alpha-1 Blocker
- Antihistamine
- Side Effect