Tricyclic Antidepressants Group Research Articles

Low concentrations of tricyclic antidepressants stimulate TRPC4 channel activity by acting as an opioid receptor ligand.

Traditionally prescribed for mood disorders, tricyclic antidepressants (TCAs) have shown promising therapeutic effects on chronic neuralgia and irritable bowel syndrome. However, the mechanism by which these atypical effects manifest is unclear. Among the proposed mechanisms is the well-known pain-related inhibitory G-protein coupled receptor, namely the opioid receptor (OR). Here, we confirmed that TCA indeed stimulates OR and regulates the gating of TRPC4, a downstream signaling of the Gi-pathway. In an ELISA to quantify the amount of intracellular cAMP, a downstream product of OR/Gi-pathway, treatment with amitriptyline (AMI) showed a decrease in [cAMP]i similar to that of the μOR agonist. Next, we explored the binding site of TCA by modeling the previously revealed ligand-bound structure of μOR. A conserved aspartate residue of ORs was predicted to participate in salt bridge interaction with the amine group of TCAs, and in aspartate-to-arginine mutation, AMI did not decrease the FRET-based binding efficiency between the ORs and Gαi2. As an alternative way to monitor the downstream signaling of Gi-pathway, we evaluated the functional activity of TRPC4 channel, as it is well known to be activated by Gαi. TCAs increased the TRPC4 current through ORs, and TCA-evoked TRPC4 activation was abolished by an inhibitor of Gαi2 or its dominant-negative mutant. As expected, TCA-evoked activation of TRPC4 was not observed in the aspartate mutants of OR. Taken together, OR could be proclaimed as a promising target among numerous binding partners of TCA, and TCA-evoked TRPC4 activation may help to explain the nonopioid analgesic effect of TCA.NEW & NOTEWORTHY Endogenous opioid systems modulate pain perception, but concerns about opioid-related substance misuse limit their use. This study has raised TRPC4 channel as a candidate target for alternative analgesics, tricyclic antidepressants (TCAs). TCAs have been shown to bind to and activate opioid receptors (ORs), leading to downstream signaling pathways involving TRPC4. The functional selectivity and biased agonism of TCA towards TRPC4 in dependence on OR may provide a better understanding of its efficacy or side effects.

Pharmacotherapy for trichotillomania.

Pharmacotherapy for trichotillomania.

Pharmaco-Electroencephalography-Based Assessment of Antidepressant Drug Efficacy-The Use of Magnesium Ions in the Treatment of Depression.

Pharmaco-electroencephalography (pharmaco-EEG) is a technique used to assess the effects of psychotropic medications on the bioelectrical activity of the brain. The purpose of this study was to assess the treatment response with the use of the Hamilton Depression Rating Scale (HDRS) and via EEG. Over an 8-week period, we analyzed electroencephalographic tracings of 91 patients hospitalized for major depression at the Medical University of Warsaw. Thirty-nine of those patients received tricyclic antidepressants (TCAs), 35 received fluoxetine, and 17 received fluoxetine augmented with magnesium (Mg) ions. All patients had their serum drug levels monitored. The highest proportion of patients (88.2%) who showed adequate responses to treatment was observed in the fluoxetine+Mg group, whereas the lowest rates of treatment response were observed in the TCA group (58.3%). This difference was statistically significant (p = 0.029, Phi = 0.30). Our study demonstrated a relationship between achieving remission (HDRS ≤ 6 at week 8 of treatment) and obtaining a positive pharmaco-EEG profile 6 h after administration of the first dose in the group receiving fluoxetine augmented with Mg ions (p = 0.035, Phi = 0.63).

Reduction in and Preventive Effects for Oral-Cancer Risk with Antidepressant Treatment.

Areca nut (AN) was identified as carcinogenic to humans. Around 600 million people globally use AN in some form, yet no effective therapeutic drug is available to overcome AN addiction. This preclinical study examines the effects of antidepressants on AN use with animal models. We produced AN powder and dissolved it into drinking water, training 55 C57BL/6 mice in free self-selection to drink AN water or normal water. Then, the mice were randomly divided into four groups. Selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs) were given as three treatment groups and one placebo group for four weeks. In the follow-up period, the preference and amount of free selection of AN and normal water, and oral pathological change were evaluated. There was a significant decrease in preference for AN drinking during the first four weeks, and the 36th week after drug withdrawal in the MAOI and SSRI groups (all p < 0.05). The drug-reducing effect of AN water in the 1–4-week period was significant in the MAOI group (p < 0.0001) and was also significant in the 3–4-week period in the SSRI group (p = 0.03). The TCA group did not show a decrease effect. At the endpoint (60 weeks), oral mucosal fibrosis (OSF) levels and risk in the SSRI (p = 0.0081) and MAOI (p = 0.01) groups were significantly lower than those in the control group. Antidepressant drugs MAOIs and SSRIs could reduce the amount of AN use and decrease the early stage of oral fibrosis in mice, but SSRIs may need to be boosted again.

Gustatory Dysfunction among a Sample of Depressed Egyptian Adults under Antidepressants Therapy: A Retrospective Cohort Study

It is quite clear that the ability to perceive taste sensations significantly affects food choice, which consequently affects health status in the long term. Gustatory dysfunction is a neglected symptom among the depressed patients and those under antidepressants therapy, although these patients are suspectable to oral problems, due to general self-negligence related to mental disease, fear of dental treatment, and side effects of varied medications utilized in psychiatry. This study is aimed at assessing gustatory thresholds (detection and recognition thresholds) among a sample of 30 depressed Egyptian adults under antidepressants therapy for at least 3 months or psychotherapy with age ranging from 20 to 50 years old, seeking the Psychiatric Clinic at the Faculty of Medicine, Cairo University, Egypt. These patients were distributed into three equal groups (tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), and psychotherapy) and were assessed for gustatory detection and recognition thresholds using the filter paper disc method through a scoring system. The participants were also divided into normal taste group in which both the detection and recognition scores were 1, while the scores from 2 till 5 were considered as hypogeusia group and the score of 6 was considered as dysgeusia group. The TCA group was statistically significant from the other 2 groups in sweet detection thresholds (p = 0.043) and sweet recognition thresholds (p = 0.007). Hypogeusia for sweet was statistically significant (p = 0.041), where it was more common among TCA (70%) than both SSRIs and the psychotherapy group (20%). Gustatory dysfunction was found to be mostly associated with TCA followed by SSRIs particularly for sweet taste thresholds. More attention has to be given to taste changes among these patients as oral health affects general health by causing considerable pain and by changing what people eat, their speech, and their quality of life and wellbeing. Proper awareness and evaluation of this problem will improve the quality of life for the depressed patients and avoid unnecessary treatment. This trial is registered with ClinicalTrials.gov ID: NCT03599011.

A 70-year history of tricyclic antidepressants

For the first time the facts from the history of tricyclic antidepressants (TCA) are systematized in Russian psychiatric literature. The authors describe the history of first TCA agents, analyze the history of TCA group development based on the increase of new agents, present the history of original TCA creation in the USSR and the Eastern block countries, systemize the history of TCA classification development and review the studies on TCA neurochemical activity. An impact of TCA history on formulation of hypotheses of the pathogenesis of depression and some forms of neuroses is demonstrated. It is shown that the history of TCA creation urged the development of new groups of antidepressants.

Anti Leishmanial Activities of Some Antidepressant Drugs and Antifungal Drugs.

Leishmanisis is wide range, worldwide, without drug, vaccine, secticide and has not sterile immunity and efforts in this field have not been successful.Leishmaniasis is a complex vectorborne disease caused by different species of Leishmania. It affects at least 12 million people worldwide. Leishmaniasis is commonly associated with poor economic conditions and immune compromised situations like HIV co infection. There is increasing in drug resistance to commonly used therapeutics as well as lack of vaccine program. This leads to a perpetual search for a new drug for leishmaniasis. This review fundamentally deals with some antidepressant drugs, and antifugal drugs showing the anti leishmanial activities. The antidepressant drugs are Imipramine, Sertraline, Ketanserin and Mianserin. Imipramine being a Tri Cyclic Antidepressant (TCA) drug kills Leishmania donovani elevating IL-12/IL-10 ratio. Sertraline belonging to the selective serotonin reuptake inhibitor (SSRI) drugs, removes parasite loads from spleen and liver probably by declining cytoplasmic ATP consumption. Ketanserin is a serotonin receptor (5HT2A/2C) antagonist that kills both amastigotes and promastigotes probably due to inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). Mianserin belonging to the TCA group of drug, kills both promastigote and amastigote parasites also probably due to the inhibition of HMGR. The present review will give the summarized information about putting some old antidepressant drugs for the treatment of another disease like Leishmania. Many topical antifungals have been available, two important antibiotics: amphotericin B to deal with systemic mycosis and griseofulvin to supplement attack on dermatophtes . A number of antifungal agents have been investigated in a rodent model for their parasiticidal activity against visceral leishmaniasis. These drugs have been administered intravenously both alone, and in conjunction with liposomes. All the compounds tested: griseofulvin, 5-fluorocytosine, and amphotericin B—together with the known antileishmanial drug pentamidine—displayed enhanced therapeutic activity when given in liposomal form. In the case of amphotericin, liposomes composed of hydrogenated lecithin, or containing cholesterol or ergosterol in the membrane, were least toxic to the mammalian host, and had the highest therapeutic capability.

A clinical study to compare hyponatremia induced by the use of two different tricyclic antidepressants – Amitriptyline and imipramine

Aims & Objectives: To compare the occurrence of hyponatremia in the patients receiving two different Tricyclic Antidepressants (TCAs)–Amitriptyline and Imipramine Methodology: Fifty OPD patients attendingthe Psychiatry outpatient clinic of Mahatma Gandhi Institute of Medical Sciences, Sewagram having diagnosis of Depressive episode as per DSM-IV-TR criteria were included in the study. Patients with normalserum sodium levels before treatment with antidepressant were included in the study. Repeat serum Sodium levels were done after one month of being on treatment. EPI Info-6 software was used to analyze the data. Results: Average serum sodium concentrations of the patients receiving different TCAs before treatment were 139.4+2.45 (Mean+SD). Out of the 44% patients who developed hyponatremia, 45.45% were amongst the Imipramine group and 54.54% were amongst the Amitriptyline group. Although of mild severity only, hyponatremia was more in patients receiving Amitriptyline compared to those receiving Imipramine. Conclusion: Patients receiving Amitriptyline have fairly more chance of developing hyponatremiathan Imipramine receiving patients. Hence precaution should be observed while using TCA group of antidepressants.

Heart rate variability in children with tricyclic antidepressant intoxication

Tricyclic antidepressant (TCA) intoxication is among the most common causes of poisonings in our country. The TCA group of drugs affects the central nervous and cardiovascular systems, resulting in severe arrhythmia and death. Heart rate variability (HRV) analysis is a non-invasive assessment method that allows evaluation of the cardiac autonomic (sympathetic and parasympathetic) activity. The aim of this study was to evaluate HRV in children requiring ICU stay due to TCA poisoning.

Microflora of the Oral Cavity in Patients with Xerostomia

The aim of this study was to evaluate the dependence of the condition of the microflora of the oral cavity on the etiology of xerostomia, patients' sex, age, degree of hyposalivation, and duration of the sense of dryness. A total of 64 patients with complaints of oral dryness referred to the Clinic of Oral and Dental Diseases, Hospital of Lithuanian University of Health Sciences, for consultation during the period from 2003 to 2005 were selected for the study. The etiological factors of xerostomia were as follows: radiotherapy (PRT) to the maxillofacial area, Sjögren's syndrome (SS), and xerogenic medications, tricyclic antidepressants (TCAs). There were 50 women and 14 men. Their mean age was 60.5 ± 1.6 years. All the patients in the PRT group had high counts of Candida spp. as compared with percentages of patients in the TCA and SS groups (100% vs. 66.7% and 56.2%, P<0.05). Patients' age and sex in different etiology groups had no significant impact on the condition of their oral microflora. There were equal percentages of patients with deficient and normal salivation in the TCA group (44% in both the groups; P<0.01). All the patients in the PRT group had pronounced hyposalivation (P<0.002). A significantly greater percentage of patients with severely reduced salivation had high counts of Lactobacillus spp. (P<0.01). Significantly greater percentages of patients with the clinical duration of xerostomia of up to 6 months had high counts of Lactobacillus spp. and Candida spp. colonies. In patients with xerostomia, the condition of the microflora of the oral cavity and impairment of major salivary gland function varied according to the etiology of the disease. The level of hyposalivation and the duration of xerostomia were found to have a significant impact on the microflora of the oral cavity.

Benzodiazepines Co-ingestion in Reducing Tricyclic Antidepressant Toxicity

Tricyclic antidepressant (TCA) overdose is generally associated with central nervous system (CNS) and cardiovascular toxicity manifested by seizure, electrocardiographic (ECG) abnormalities and arrhythmia. The objective of this study was to determine whether TCA toxicity would be reduced in patient where benzodiazepine (BDZ) was co-ingested with TCA. Patients who were diagnosed to be poisoned by ingestion of both a tricyclic antidepressant and benzodiazepine (TCA-BDZ), and patients intoxicated solely by a TCA were assessed, provided that they had one or more clinical signs of toxicity (anticholinergic, cardiovascular or CNS findings) and no underlying cardiac disease. TCA poisoned patients who had ingested any drugs other than benzodiazepines were excluded. Patients transferred from elsewhere and those admitted after the first 24 hours were also excluded. The clinical manifestations of TCA toxicity and outcome of the patients poisoned only with TCA (N = 60) were compared with those of the patients who had co-ingested TCAs and BDZs (N = 60). The frequency distribution of sinus tachycardia, "QRS more than 100 ms, R/S aVR equal or more than 0.7, RaVR equal or more than 3 mm", arrhythmia, and generalized tonic colonic seizure was less in patients who had co-ingested BDZ with TCA. Evaluating the relationship between ingested TCA dosage and electrocardiographic findings (duration of QRS, QT and PR intervals, the amplitude of R wave in lead aVR and right axis deviation) in both study groups, demonstrated that there was a strong relationship between TCA dosage and QRS duration in the TCA group. This was significantly different from the same correlation in the TCA-BDZ group (r, 0.50 in TCA group versus r, 0.04 in TCA and BDZ group, P < 0.05). No significant differences were found in complications (aspiration pneumonia, non-cardiac pulmonary oedema and death) between the two groups. cardiovascular toxicity and seizure may be less in TCA-BDZ poisoned patients compared with patients intoxicated with TCA-alone.

Rapid improvement of depressive symptoms in suicide attempters following treatment with milnacipran and tricyclic antidepressants &amp;ndash; a case series

Suicide is a serious social problem in many countries, including Japan. The majority of people who commit suicide suffer from depression. Suicide attempt patients suffering from serious physical injuries are initially treated in hospital emergency departments. The present post hoc analysis examined data from patients admitted to an emergency hospital for treatment of physical injuries, resulting from a suicide attempt, and initial psychiatric treatment for depression and prevention of future suicide attempts. The effects on depressive symptoms were studied in two groups of patients using the 17-item Hamilton depression scale (HAMD). One group (n = 6) had received intravenous tricyclic antidepressants (TCA) (amitriptyline or clomipramine) while the other group (n = 7) had been treated orally with milnacipran, a serotonin and norepinephrine reuptake inhibitor antidepressant. Prior to treatment the four highest scoring items on the HAMD scale were the same in both groups namely, item 1 (depressed mood), item 3 (suicidality), item 7 (interest in work and activities), and item 10 (psychic anxiety). After 1 week of treatment, mean global HAMD scores were significantly reduced in both groups. Treatment resulted in a significant reduction of five HAMD items in the TCA group, whereas in the milnacipran group 12 HAMD items were significantly reduced. Suicidality (item 3) was significantly improved by 1 week treatment with milnacipran, but not by TCAs. Milnacipran rapidly improved a wide range of depressive symptoms, including suicidality within the first week. The improvement with milnacipran would appear to be, at least, equivalent to that achieved with TCAs, possibly affecting a wider range of symptoms. Since milnacipran has been shown in comparative studies to be better tolerated than TCAs, this antidepressant offers an interesting option for the treatment of suicidal patients in an emergency setting.

Changing Epidemiology of Intentional Antidepressant Drug Overdose in Victoria, Australia

To determine the epidemiology of intentional antidepressant drug overdose (OD), over an extended time period, in Victoria, Australia. Retrospective epidemiological study of all cases reported to the Victorian Emergency Minimum Dataset (VEMD) January 1998 to December 2007 and calls to the Victorian Poisons Information Centre (VPIC) June 2005 to September 2008. 5467 VEMD cases were analysed. 3169 (57.9%) cases involved selective serotonin reuptake inhibitors (SSRIs) and 1149 (21%) involved tricyclic antidepressants (TCAs). Sertraline (1252, 22.9% cases) was the most common drug. During 2001, the peak year of OD, there were 8.8 OD/100 000 population in the SSRI group and 3.8 OD/100 000 population in the TCA group. Trends over the study period showed increasing SSRI and 'other' newer antidepressant prescription rates and decreases for TCA and monoamine oxidase inhibitors (MAOI). However, the risks of OD in all drug classes were similar and OD/100 000 prescriptions trended downwards for all drug classes over time. 1833 VPIC calls were analysed. Calls relating to SSRIs were the most common yet SSRI OD was associated with significantly fewer symptoms (p < 0.001) and fewer patients with Poisoning Severity Score classifications of moderate or severe (p < 0.01). Antidepressant OD patterns are changing. Antidepressant OD incidence is following prescribing trends. The risk of OD is similar for all drug classes. Absolute numbers of OD and OD/100 000 prescriptions are decreasing for all drug classes.

Effects of antidepressant treatments on first-ect seizure duration in depression

1. Current guidelines on the practice of Electroconvulsive Therapy (ECT) suggest that antidepressant medications should be discontinued prior to the course of therapy. However, the practice of withholding potentially helpful medication is debatable because the effects of these medications on seizure duration remain unclear. In particular, there is a lack of emperical knowledge about the effects of Selective Serotonin Reuptake Inhibitors (SSRIs) on ECT treatment. 2. Therefore, we investigated and compared the effects of SSRIs and tricyclic antidepressants (TCAs) on seizure duration after the first bilateral ECT treatment. 3. The diagnosis of major depressive disorder was made using the DSM-IV criteria. Both patients groups were age- and sex-matched. ECT was indicated for acute suicidal acts or refractoriness to medications. All patients had received antidepressant treatment for at least eight weeks and were receiving at least the recommended dose of medication. All patients were ECT treatment-naïve and we measured the seizure duration after the first bilateral ECT treatment. 4. There was no significant difference between electrical charge applied to either group. Between the TCA and SSRI group the seizure duration was not significantly different: 33.2 seconds and 31.4 seconds respectively.

Selective serotonin reuptake inhibitors have broadened the utilisation of antidepressant treatment in accordance with recommendations: Findings from a Swedish prescription database

Background: With the advent of the selective serotonin reuptake inhibitors (SSRIs), the use of antidepressants has increased drastically in Sweden. The use of tricyclic antidepressants (TCAs) has, however, decreased. Methods: We surveyed a prescription database in the Swedish county of Jämtland and compared prescription patterns for patients prescribed SSRIs with those prescribed TCAs. Results: The incidence of treatments of antidepressants increased from 0.76% to 1.33% during the period 1991–1996. There were no significant differences between SSRIs and TCAs with regard to patients having only one prescription dispensed within three months from the index prescription, or patients who switched class of antidepressant. Only a minority of the treatments were continued for at least six months, but significantly more SSRI than TCA treatments (42% and 27%). A second treatment period suggesting recurrence was three-times more common in the TCA group than in the SSRI group. Conclusion: Provided that the increased use of SSRIs is mainly for depression, these drugs appear, despite a lower efficacy in severe depression, to have enabled a broader utilisation of antidepressants with regard to incidence, dosage and duration, in accordance with recommendations. Further analyses of this phenomenon relative to diagnostic criteria and outcome measures are required.

CARDIOVASCULAR EFFECTS OF POISONING WITH TRICYCLIC ANTIDEPRESSANTS

Abstract. Cardiovascular dynamics have been studied in 10 patients admitted because of poisoning by tricyclic antidepressants (TCA) and in 7 with hypnotic drug (HD) poisoning. Right heart catheterization (floating catheter technique) and determination of cardiac output (dye dilution technique) have been performed during and after an initial comatous phase. In the TCA group there were marked ECG changes with a mean increase of QRS duration to 0.14 sec during the comatous phase. The cardiac output was then increased in relation to the calculated oxygen uptake compared with the findings in awake state, when the ECG changes had diminished or disappeared. After i.v. administration of 5 mg propranolol the fall in cardiac output was most pronounced during the comatous phase but the broadening of QRS complexes was not affected. The central venous and systemic arterial BP were normal. As judged by the normal diastolic pressure in the pulmonary artery and the normal central venous pressure there were no signs of myocardial insufficiency. The cardiac output in the TCA group was twice as high, i.e. significantly higher, as in the HD patients. The arteriovenous oxygen difference was significantly lower (on an average 40%). The hyperkinetic circulation during TCA poisoning may be explained by a dominant adrenergic stimulatory effect on the circulation.