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The Journal of Clinical Psychiatry Apr 2007Depression with atypical features is characterized by mood reactivity and 2 or more symptoms of vegetative reversal (including overeating, oversleeping, severe fatigue... (Review)
Review
Depression with atypical features is characterized by mood reactivity and 2 or more symptoms of vegetative reversal (including overeating, oversleeping, severe fatigue or leaden paralysis, and a history of rejection sensitivity). Another important feature of atypical depression is its preferential response to monoamine oxidase inhibitor (MAOI) treatment, especially phenelzine, relative to tricyclic antidepressants (TCAs). The efficacy of newer agents relative to MAOIs and TCAs is unclear. This presentation reviews currently available treatments for DSM-IV depression with atypical features, focusing specifically on placebo-controlled trials. Although phenelzine shows the most efficacy in this population, treatment with TCAs, selective serotonin reuptake inhibitors, cognitive-behavioral therapy, MAOIs other than phenelzine, and other agents are discussed. Following this presentation is a discussion on the treatment of depression with atypical features by experts in this subject area.
Topics: Antidepressive Agents, Tricyclic; Depressive Disorder; Diagnostic and Statistical Manual of Mental Disorders; Humans; Monoamine Oxidase Inhibitors; Phenelzine
PubMed: 17474800
DOI: 10.4088/jcp.0407e10 -
Cellular and Molecular Neurobiology Jan 2022Phenelzine (PLZ) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. This multifaceted drug has a number of pharmacological and... (Review)
Review
Phenelzine (PLZ) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. This multifaceted drug has a number of pharmacological and neurochemical effects in addition to inhibition of MAO, and findings on these effects have contributed to a body of evidence indicating that PLZ also has neuroprotective/neurorescue properties. These attributes are reviewed in this paper and include catabolism to the active metabolite β-phenylethylidenehydrazine (PEH) and effects of PLZ and PEH on the GABA-glutamate balance in brain, sequestration of reactive aldehydes, and inhibition of primary amine oxidase. Also discussed are the encouraging findings of the effects of PLZ in animal models of stroke, spinal cord injury, traumatic brain injury, and multiple sclerosis, as well other actions such as reduction of nitrative stress, reduction of the effects of a toxin on dopaminergic neurons, potential anticonvulsant actions, and effects on brain-derived neurotrophic factor, neural cell adhesion molecules, an anti-apoptotic factor, and brain levels of ornithine and N-acetylamino acids.
Topics: Animals; Antidepressive Agents; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neuroprotective Agents; Phenelzine; Rats; Rats, Sprague-Dawley
PubMed: 33839994
DOI: 10.1007/s10571-021-01078-3 -
The Cochrane Database of Systematic... Jun 2010Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders ("off-label use"), mostly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders ("off-label use"), mostly targeting affective or impulsive symptom clusters.
OBJECTIVES
To assess the effects of drug treatment in BPD patients.
SEARCH STRATEGY
We searched bibliographic databases according to the Cochrane Developmental, Psychosocial and Learning Problems Group strategy up to September 2009, reference lists of articles, and contacted researchers in the field.
SELECTION CRITERIA
Randomised studies comparing drug versus placebo, or drug versus drug(s) in BPD patients. Outcomes included total BPD severity, distinct BPD symptom facets according to DSM-IV criteria, associated psychopathology not specific to BPD, attrition and adverse effects.
DATA COLLECTION AND ANALYSIS
Two authors selected trials, assessed quality and extracted data, independently.
MAIN RESULTS
Twenty-eight trials involving a total of 1742 trial participants were included. First-generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second-generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega-3 fatty acid) were tested. First-generation antipsychotics were subject to older trials, whereas recent studies focussed on second-generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first-generation antipsychotics and antidepressants.The findings were suggestive in supporting the use of second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but require replication, since most effect estimates were based on single studies. The long-term use of these drugs has not been assessed.Adverse event data were scarce, except for olanzapine. There was a possible increase in self-harming behaviour, significant weight gain, sedation and changes in haemogram parameters with olanzapine. A significant decrease in body weight was observed with topiramate treatment. All drugs were well tolerated in terms of attrition.Direct drug comparisons comprised two first-generation antipsychotics (loxapine versus chlorpromazine), first-generation antipsychotic against antidepressant (haloperidol versus amitriptyline; haloperidol versus phenelzine sulfate), and second-generation antipsychotic against antidepressant (olanzapine versus fluoxetine). Data indicated better outcomes for phenelzine sulfate but no significant differences in the other comparisons, except olanzapine which showed more weight gain and sedation than fluoxetine. The only trial testing single versus combined drug treatment (olanzapine versus olanzapine plus fluoxetine; fluoxetine versus fluoxetine plus olanzapine) yielded no significant differences in outcomes.
AUTHORS' CONCLUSIONS
The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).
Topics: Antidepressive Agents; Antipsychotic Agents; Borderline Personality Disorder; Fatty Acids, Omega-3; Humans; Randomized Controlled Trials as Topic
PubMed: 20556762
DOI: 10.1002/14651858.CD005653.pub2 -
British Medical Journal May 1977
Topics: Depression; Edema; Female; Humans; Middle Aged; Phenelzine
PubMed: 861629
DOI: 10.1136/bmj.1.6072.1353-a -
British Medical Journal Oct 1969
Topics: Adult; Female; Humans; Lactation Disorders; Personality Disorders; Phenelzine; Pregnancy
PubMed: 5388733
DOI: 10.1136/bmj.4.5677.236-a -
Experimental Neurology Aug 2020Traumatic brain injury (TBI) results in mitochondrial dysfunction and induction of lipid peroxidation (LP). Lipid peroxidation-derived neurotoxic aldehydes such as 4-HNE... (Review)
Review
Protective effects of phenelzine administration on synaptic and non-synaptic cortical mitochondrial function and lipid peroxidation-mediated oxidative damage following TBI in young adult male rats.
Traumatic brain injury (TBI) results in mitochondrial dysfunction and induction of lipid peroxidation (LP). Lipid peroxidation-derived neurotoxic aldehydes such as 4-HNE and acrolein bind to mitochondrial proteins, inducing additional oxidative damage and further exacerbating mitochondrial dysfunction and LP. Mitochondria are heterogeneous, consisting of both synaptic and non-synaptic populations, with synaptic mitochondria being more vulnerable to injury-dependent consequences. The goal of these studies was to explore the hypothesis that interrupting secondary oxidative damage following TBI using phenelzine (PZ), an aldehyde scavenger, would preferentially protect synaptic mitochondria against LP-mediated damage in a dose- and time-dependent manner. Male Sprague-Dawley rats received a severe (2.2 mm) controlled cortical impact (CCI)-TBI. PZ (3-30 mg/kg) was administered subcutaneously (subQ) at different times post-injury. We found PZ treatment preserves both synaptic and non-synaptic mitochondrial bioenergetics at 24 h and that this protection is partially maintained out to 72 h post-injury using various dosing regimens. The results from these studies indicate that the therapeutic window for the first dose of PZ is likely within the first hour after injury, and the window for administration of the second dose seems to fall between 12 and 24 h. Administration of PZ was able to significantly improve mitochondrial respiration compared to vehicle-treated animals across various states of respiration for both the non-synaptic and synaptic mitochondria. The synaptic mitochondria appear to respond more robustly to PZ treatment than the non-synaptic, and further experimentation will need to be done to further understand these effects in the context of TBI.
Topics: Animals; Brain Injuries, Traumatic; Cerebral Cortex; Lipid Peroxidation; Male; Mitochondria; Neuroprotective Agents; Oxidative Stress; Phenelzine; Rats; Rats, Sprague-Dawley; Synapses
PubMed: 32325157
DOI: 10.1016/j.expneurol.2020.113322 -
Journal of Psychiatry & Neuroscience :... Nov 2000Antidepressants, in addition to being effective therapeutic agents for depression, have also proved to be multifaceted drugs useful for treating a number of other... (Review)
Review
Antidepressants, in addition to being effective therapeutic agents for depression, have also proved to be multifaceted drugs useful for treating a number of other psychiatric and neurologic disorders. Despite the widespread use of these drugs, much remains to be understood about their mechanisms of action and other important aspects, such as their metabolism and potential interactions with other drugs. This article reviews research conducted in the authors' laboratories on various aspects of antidepressants, including trace amines and antidepressants, gamma-aminobutyric acid and antidepressants, drug metabolism, development and application of rapid, sensitive assay procedures for antidepressants and their metabolites; and drug development based on analogues of the antidepressants phenelzine and tranylcypromine. The significance of this work to future drug development is also discussed.
Topics: Animals; Antidepressive Agents; Biogenic Amines; Biological Assay; Brain Chemistry; Cytochrome P-450 Enzyme System; Drug Design; Humans; gamma-Aminobutyric Acid
PubMed: 11109299
DOI: No ID Found -
Anaesthesia Jul 1964
Review
Topics: Amphetamine; Amphetamines; Anesthesia; Anesthetics; Antidepressive Agents; Chlorpromazine; Ephedrine; Ergotamine; Hydrazines; Hypnotics and Sedatives; Iproniazid; Isocarboxazid; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Nialamide; Pharmacology; Phenelzine; Phentolamine; Prednisolone; Procaine; Serotonin; Toxicology; Tranylcypromine; Vasopressins
PubMed: 14174638
DOI: 10.1111/j.1365-2044.1964.tb00392.x -
Frontiers in Oncology 2022Lysine-Specific Demethylase-1 (LSD1) is overexpressed in breast cancer cells and facilitate mesenchymal properties which may contribute to therapeutic resistance and...
OBJECTIVE
Lysine-Specific Demethylase-1 (LSD1) is overexpressed in breast cancer cells and facilitate mesenchymal properties which may contribute to therapeutic resistance and cancer progression. The purpose of this study was to investigate the safety of combination, nab-paclitaxel and phenelzine, an irreversible LSD1 inhibitor in patients with metastatic breast cancer (mBC).
METHODS
Eligible patients with mBC were treated with nab-paclitaxel (100mg/m) weekly for 3 weeks with one week break in a 28-day cycle. Dose escalation of phenelzine followed the Cumulative Cohort Design and phenelzine treatment commenced from day 2 of first cycle. Eleven patients were screened, and eligible patients were enrolled in cohorts with the dose of phenelzine ranging from 45mg to 90mg.
RESULTS
The Optimum Biological Dose was established at 60mg of phenelzine daily in combination with nab-paclitaxel and considered as the recommended phase 2 dose. Most (95%) of adverse events were grade 1 or 2 with two grade 3 events being diarrhea and neutropenia at 45mg and 60mg phenelzine respectively, with no unexpected toxicity/deaths. Commonly reported toxicities were fatigue (n=4,50%), dizziness (n=6,75%), neutropenia (n=3,37.5%), peripheral neuropathy (n=3,37.5%), diarrhea (n=2,25%), and hallucination (n=2,25%). After a median follow up of 113 weeks, all patients showed disease progression on trial with 4 patients being alive at the time of data cut off, including one patient with triple negative breast cancer. Median progression-free survival was 34 weeks. Significant inhibition of LSD1 and suppression of mesenchymal markers in circulating tumor cells were noted.
CONCLUSION
Phenelzine in combination with nab-paclitaxel was well tolerated, without any unexpected toxicities in patients with mBC and demonstrated evidence of antitumor activity. For the first time, this proof-of-concept study showed inhibition of LSD1 suppressed mesenchymal markers, which are known to facilitate generation of cancer stem cells with metastatic potential. ClinicalTrials.Gov NCT03505528, UTN of U1111-1197-5518.
PubMed: 35719960
DOI: 10.3389/fonc.2022.862427 -
Photodermatology, Photoimmunology &... May 2023Lysine-specific histone demethylase 1 (KDM1A/LSD1) regulates multiple cellular functions, including cellular proliferation, differentiation, and DNA repair. KDM1A is...
BACKGROUND
Lysine-specific histone demethylase 1 (KDM1A/LSD1) regulates multiple cellular functions, including cellular proliferation, differentiation, and DNA repair. KDM1A is overexpressed in squamous cell carcinoma of the skin and inhibition of KDM1A can suppress cutaneous carcinogenesis. Despite the role of KDM1A in skin and DNA repair, the effect of KDM1A inhibition on cellular ultraviolet (UV) response has not been studied.
METHODS
The ability of KDM1A inhibitor bizine to modify cell death after UVA and UVB exposure was tested in normal human keratinocytes and melanocytes, HaCaT, and FaDu cell lines. KDM1A was also downregulated using shRNA and inhibited by phenelzine in HaCaT and FaDu cells to confirm the role of KDM1A in UVA response. In addition, cellular reactive oxygen species (ROS) changes were assessed by a lipid-soluble fluorescent indicator of lipid oxidation, and ROS-related gene regulation using qPCR. During photodynamic therapy (PDT) studies HaCaT and FaDu cells were treated with aminolaevulinic acid (5-ALA) or HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) sodium and irradiated with 0-8 J/cm red LED light.
RESULTS
KDM1A inhibition sensitized cells to UVA radiation-induced cell death but not to UVB. KDM1A inhibition increased ROS generation as detected by increased lipid peroxidation and the upregulation of ROS-responsive genes. The effectiveness of both ALA and HPPH PDT significantly improved in vitro in HaCaT and FaDu cells after KDM1A inhibition.
CONCLUSION
KDM1A is a regulator of cellular UV response and KDM1A inhibition can improve PDT efficacy.
Topics: Humans; Aminolevulinic Acid; Histone Demethylases; Keratinocytes; Lipids; Photochemotherapy; Reactive Oxygen Species; Skin; Ultraviolet Rays
PubMed: 35968606
DOI: 10.1111/phpp.12826