Efficacy of Nortriptyline and Migraine Lifestyle Modifications in Vestibular Migraine Management.

OBJECTIVE: To evaluate the effectiveness of nortriptyline regimen and migraine dietary/lifestyle modifications on dizziness and stress levels in patients diagnosed with vestibular migraine (VM). METHODS: A total of 35 patients diagnosed with definite VM based on the International Classification of Headache Disorders were included in this intervention study. Patients self-selected to receive either nortriptyline regimen alone (10-40 mg daily with biweekly escalation) (group A, n = 17) or migraine dietary/lifestyle modifications alone (group B, n = 18). Main outcome measures were dizziness severity and stress level measured by the visual analog scale (VAS). RESULTS: At 4-week post-treatment, dizziness decreased from 6.0 ± 2.5 to 4.2 ± 3.4 (p = 0.069) in group A and from 8.7 ± 1.5 to 3.6 ± 3.0 (p < 0.001) in group B. VAS for stress changed from 5.5 ± 1.3 to 5.4 ± 2.9 (p = 0.93) and from 6.9 ± 3.2 to 5.0 ± 2.7 (p = 0.025) in groups A and B, respectively. The δ values of the VAS score for dizziness were 1.8 ± 3.7 and 5.1 ± 3.1 and the δ values of the VAS score for stress were 0.06 ± 2.9 and 1.9 ± 3.3 in groups A and B, respectively. Quality of life (QOL) improved in 88% patients in group A and 94% patients in group B. CONCLUSIONS: Nortriptyline, at a maximum dose of 40 mg, effectively alleviates patient symptoms, while a migraine diet and lifestyle modifications notably reduce vertiginous symptoms and stress levels in VM patients in 4 weeks. Both interventions are equally effective in ameliorating the QOL of patients. The ideal treatment for patients would likely need to include both medication and diet/lifestyle changes.

Persistent Idiopathic Dentoalveolar Pain in a Patient With Implant Placement: A Case Report.

Persistent idiopathic dentoalveolar pain (PIDAP) is a type of disease that, despite affecting thousands of people globally, negatively impacts patients' quality of life because of its unknown cause. Notably, the disease has a high prevalence rate and is primarily prone to middle-aged and senior individuals. Efforts have been made to gain the understanding needed for the accurate diagnosis and prompt treatment of PIDAP cases. This case report discusses the challenges faced in diagnosing and managing PIDAP after dental implants. The present study involved the case of a 62-year-old male patient, previously operated on for an implant at position #11, who suffered from chronic pain but no specific cause could be identified. We used an evaluation strategy to gain insights into the patient's illness, including antibiotic treatment, crown replacement, and continued pain. We prescribed nortriptyline 10 mg, and there was an improvement. This finding suggests that nortriptyline 10 mg QHS eliminates chronic pain.

Efficacy and safety of cytisine versus nortriptyline for smoking cessation: A multicentre, randomized, double-blinded and placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Cytisine serves as an affordable smoking cessation aid with acceptable safety profile. However, data comparing its efficacy and safety to standard therapies are limited. We aimed to examine efficacy and safety of cytisine compared to nortriptyline, which is the only approved smoking-cessation medication in Thailand. METHODS: A 12-month, multicentre, randomized, double-blinded, placebo-controlled trial was conducted. Participants aged ≥20 years who smoked ≥10 cigarettes/day were randomly assigned to receive a 25-day cytisine or a 12-week nortriptyline treatment course. Brief interventions (BI) for smoking cessation were provided to all participants. The primary outcome was biochemically verified continuous abstinence rate (CAR) at 12 months. Additionally, self-reported abstinence, verified by exhaled carbon monoxide (CO) ≤ 10 ppm, was collected at 2 weeks, 1, 3, 6 and 12 months to assess both CAR and 7-day point prevalence abstinence rate (PAR). RESULTS: A total of 1086 participants were recruited and randomized into cytisine (n = 540) and nortriptyline (n = 546) groups. The 12-month CAR was 12.22% for cytisine and 9.52% for nortriptyline. The relative difference was 0.03 (95% confidence interval [CI]; -0.01 to 0.06) and the relative risk was 1.28 (95% CI; 0.91-1.81). No differences were observed in secondary outcomes between both groups. The incidence of adverse effects from cytisine appeared to be lower than that of nortriptyline. CONCLUSION: At 12 months, cytisine plus BI was as effective as nortriptyline plus BI for smoking cessation. The adverse events for both cytisine and nortriptyline were minimal and well-tolerated.

Efficacy and safety of venlafaxine versus nortriptyline for the preventive treatment of migraine: A double-blind randomized clinical trial.

OBJECTIVE: Migraine, as a primary headache disorder, stands as one of the primary causes of disability worldwide. Consequently, prophylactic treatments are highly recommended for individuals experiencing recurrent migraine episodes. Our study aimed to compare the efficacy and safety profiles of venlafaxine and nortriptyline in the prophylactic management of migraine. METHODS: In this single-center, randomized, double-blind clinical trial, 210 migraine patients were allocated into two groups in a 1:1 ratio. One group received venlafaxine (37.5 mg, orally twice daily), while the other group administered nortriptyline (25 mg, orally once daily). A neurologist documented (1) headache intensity using the Visual Analog Scale (VAS) and 6-point Behavioral Rating Scale (BRS-6), (2) headache frequency (per month), and (3) headache duration (in hours) of participants on days 0, 45, and 90 of the intervention. RESULTS: Following the 90-day intervention, a significant decrease was observed in VAS, BRS-6, frequency, and duration of headaches within both groups (all with p-values <0.001). No difference in VAS, BRS-6, or headache durations was observed between the two groups after 45 and 90 days of treatment (all p-values > 0.05). Although the headache frequency exhibited no difference between the groups after 45 days (p-value = 0.097), a significantly lower frequency in the venlafaxine group was observed at day 90 of the intervention (p-value = 0.011). The reductions in attack parameters in the 0-45- and 0-90-day intervals did not meet statistical significance between the two groups (p-values > 0.05). 77.0 % of the participants in the venlafaxine group and 79.2 % in the nortriptyline group experienced a minimum of 50 % improvement in all attack parameters. Venlafaxine demonstrated a statistically significant lower incidence of adverse reactions in comparison to nortriptyline (p-value = 0.005). A total of 33 adverse drug reactions were documented in the venlafaxine group and 53 in the nortriptyline group, with insomnia observed in the former and xerostomia in the latter as the most prevalent side effects. CONCLUSIONS: Venlafaxine and nortriptyline demonstrate clinically significant and comparable therapeutic efficacy for migraine patients in reducing the intensity, frequency, and duration of headache attacks. Venlafaxine may be preferred to nortriptyline in the context of migraine preventive treatment under comparable conditions due to its lower incidence of adverse effects.

Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway.

Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)-NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.

Nortriptyline-Induced Room Tilt Illusion.

Room tilt illusion (RTI) is a rare and transient perceptual disturbance in which an individual perceives their surroundings as having been rotated or tilted, usually at 90 or 180 degrees. Primarily linked with vestibular disorders and neurological lesions, this report details the only reported occurrence of the RTI phenomena in nortriptyline use for treatment-refractory depression. The patient developed RTI six days after starting the medication and the disturbance resolved after medication cessation. Although the mechanism behind such a phenomenon with medication use has not been elucidated, its etiology may rest on the effect of tricyclic antidepressants on the vestibulo-thalamo-cortical system and visual-vestibular integration. Clinicians should be aware of the potential for such a medication-induced perceptual disturbance, especially in the workup for more serious etiologies in elderly patients with co-morbidities.

Clinical Trial: Efficacy of Mosapride Controlled-release and Nortriptyline in Patients With Functional Dyspepsia: A Multicenter, Double-placebo, Double-blinded, Randomized Controlled, Parallel Clinical Study.

Background/Aims: Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment. Methods: Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life. Results: One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline. Conclusion: Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.

Obstructive Sleep Apnea and Smoking Increase the Risk of Cardiovascular Disease: Smoking Cessation Pharmacotherapy.

Tobacco smoking has been a recognized risk factor for cardiovascular diseases (CVD). Smoking is a chronic relapsing disease and pharmacotherapy is a main component of smoking cessation. Obstructive sleep apnea (OSA) and smoking both increase the risk of CVD and are associated with significant morbidity and mortality. There are few existing data examining how pharmacological treatment, such as nicotine replacement therapy (NRT), bupropion, and varenicline, affect smokers suffering with OSA and especially their cardiovascular effects. The aim of this review was to evaluate the effects of smoking cessation pharmacotherapy on OSA with a special emphasis on the cardiovascular system. Results: Only small studies have assessed the effect of NRTs on OSA. Nicotine gum administration showed an improvement in respiratory events but with no permanent results. No specific studies were found on the effect of bupropion on OSA, and a limited number evaluated varenicline's effects on sleep and specifically OSA. Varenicline administration in smokers suffering from OSA reduced the obstructive respiratory events, especially during REM. Studies on second-line medication (nortriptyline, clonidine, cytisine) are even more limited. There are still no studies evaluating the cardiovascular effects of smoking cessation medications on OSA patients. Conclusions: Sleep disturbances are common withdrawal effects during smoking cessation but could be also attributed to pharmacotherapy. Smokers should receive personalized treatment during their quitting attempts according to their individual needs and problems, including OSA. Future studies are needed in order to evaluate the efficacy and safety of smoking cessation medications in OSA patients.

Cyclodextrin's Effect on Permeability and Partition of Nortriptyline Hydrochloride.

Cyclodextrin-based delivery systems have been intensively used to improve the bioavailability of drugs through the modification of their pharmaceutically relevant properties, such as solubility, distribution and membrane permeation. The present work aimed to disclose the influence of HP-ß-CD and SBE-ß-CD on the distribution and permeability of nortriptyline hydrochloride (NTT•HCl), a tricyclic antidepressant drug. To this end, the distribution coefficients in the 1-octanol/buffer and n-hexane/buffer model systems and the coefficients of permeability through the cellulose membrane and lipophilic PermeaPad barrier were determined at several cyclodextrin concentrations. The results demonstrated a dramatic decrease in both the distribution and the permeability coefficients as the cyclodextrin concentration rose, with the decrease being more pronounced in SBE-ß-CD due to the charge-charge attraction and electrostatic interactions between NTT and SBE-ß-CD. It is these interactions that were shown to be responsible for the greater value of the constant of NTT's association with SBE-ß-CD than that with HP-ß-CD. The findings of this study revealed similar trends in the 1-octanol/buffer 6.8 pH distribution and permeability through the PermeaPad barrier in the presence of CDs. These results were attributed to the determinative role of the distribution coefficient (serving as a descriptor) in permeation through the PermeaPad barrier modeling the lipophilic nature of biological barriers.

Tricyclic antidepressants induce liver inflammation by targeting NLRP3 inflammasome activation.

BACKGROUND: Idiosyncratic drug-induced liver injury (IDILI) is common in hepatology practices and, in some cases, lethal. Increasing evidence show that tricyclic antidepressants (TCAs) can induce IDILI in clinical applications but the underlying mechanisms are still poorly understood. METHODS: We assessed the specificity of several TCAs for NLRP3 inflammasome via MCC950 (a selective NLRP3 inhibitor) pretreatment and Nlrp3 knockout (Nlrp3-/-) BMDMs. Meanwhile, the role of NLRP3 inflammasome in the TCA nortriptyline-induced hepatotoxicity was demonstrated in Nlrp3-/- mice. RESULTS: We reported here that nortriptyline, a common TCA, induced idiosyncratic hepatotoxicity in a NLRP3 inflammasome-dependent manner in mildly inflammatory states. In parallel in vitro studies, nortriptyline triggered the inflammasome activation, which was completely blocked by Nlrp3 deficiency or MCC950 pretreatment. Furthermore, nortriptyline treatment led to mitochondrial damage and subsequent mitochondrial reactive oxygen species (mtROS) production resulting in aberrant activation of the NLRP3 inflammasome; a selective mitochondrial ROS inhibitor pretreatment dramatically abrogated nortriptyline-triggered the NLRP3 inflammasome activation. Notably, exposure to other TCAs also induced aberrant activation of the NLRP3 inflammasome by triggering upstream signaling events. CONCLUSION: Collectively, our findings revealed that the NLRP3 inflammasome may act as a crucial target for TCA agents and suggested that the core structures of TCAs may contribute to the aberrant activation of NLRP3 inflammasome induced by them, an important factor involved in the pathogenesis of TCA-induced liver injury. Video Abstract.

Comparison of the potency of nortriptyline and mirtazapine on gastrointestinal symptoms, the level of anxiety and depression in patients with functional dyspepsia.

Aim: In the current clinical trial study, the potency of mirtazapine and nortriptyline was compared in patients with Functional Dyspepsia (FD) who had anxiety or depression. Background: FD usually accompanies other psychosocial disorders. According to previous studies, among these disorders, anxiety and depression have the most correlation. Methods: This randomized clinical trial was organized in Taleghani hospital (Tehran, Iran). In two parallel groups, 42 patients were treated for 12 weeks, with 22 patients receiving 7.5 mg of mirtazapine and 20 patients receiving 25 mg of nortriptyline per day. To gain robust results, the patients with a positive history of antidepressant therapy, organic diseases, alcohol abuse, pregnancy, and major psychiatric disorders were excluded from the study. The subjects were examined by three questionnaires, including Nepean and Hamilton questionnaires. The patients were asked to answer the questions three times during the study: once before the onset of the treatment, second during the treatment, and third at the end of the treatment. Results: Based on Gastrointestinal (GI) manifestations, mirtazapine, in comparison to nortriptyline could significantly suppress the signs and symptoms of FD, including epigastric pains (P=0.02), belching (P=0.004), and bloating (P=0.01). Although the results from the use of mirtazapine compared to the use of nortriptyline (P=0.002) showed a lower mean depression score on the Hamilton questionnaire, no significant differences were found between the effects of these drugs on the anxiety scale of patients (P=0.091). Conclusion: Mirtazapine is more effective for GI symptoms related to gastric emptying. Considering the level of anxiety, mirtazapine, compared to nortriptyline, revealed better outcomes in FD patients suffering from depression.

Pharmacotherapy in Tobacco Cessation: A Narrative Review.

A chronic, recurring illness, known as nicotine addiction and dependence, is defined by a person's dependence on the substance up to the extent that their normal day-to-day activities are compromised in the absence of the substance. This paper will highlight first-line smoking cessation treatments, such as nicotine replacement therapy (NRT), bupropion, and varenicline, and second-line medications, such as clonidine, nortriptyline, anxiolytics, mecamylamine, naltrexone, and NicVAX (Nabi Biopharmaceuticals, Rockville, MD, USA). NRT offers many options for nicotine delivery methods, comprising nicotine gum, rapid-release gum, lozenges, transdermal patches, high-dose nicotine patches, oral inhalers, nasal sprays, electronic nicotine delivery systems (ENDS), and sublingual tablets. Pharmacotherapies for quitting tobacco should lessen withdrawal symptoms and stop nicotine's reinforcing effects without having too many side effects.

Antinociceptive effects of nortriptyline and desipramine hydrochloride in Speke's hinge-back tortoise (Kinixys Spekii).

Some of the most commonly used analgesic drugs in animals are of questionable efficacy or present adverse side effects among the various species of reptiles. Tricyclic antidepressants have been demonstrated to have antinociceptive effects in several animal models of pain and could be a good alternative for use in reptiles. The aim of the study was to investigate the antinociceptive effects of nortriptyline and desipramine hydrochloride in Speke's hinge-back tortoise. A total of 24 animals weighing 600-1000 g were used for nociceptive tests, i.e., formalin, capsaicin, and hot plate tests. Drugs were administered intracoelomically 30 min before starting the tests. The time spent in nocifensive behavior and the associated observable effects during the tests were recorded. Only the highest dose of 40 mg/kg of nortriptyline hydrochloride caused statistically significant decrease in nocifensive behavior in both the formalin and the capsaicin test. Desipramine hydrochloride at doses of 20 and 40 mg/kg caused statistically significant decrease in nocifensive behavior in the formalin test. Also, desipramine hydrochloride at doses of 15, 20, and 60 mg/kg caused statistically significant decrease in nocifensive behavior in the capsaicin test. None of the doses used for both drugs had any statistically significant effect on nocifensive behavior in the hot plate test. The results show that nortriptyline and desipramine hydrochloride have significant antinociceptive effects in the chemical but not thermal inflammatory pain-related behavior in the Speke's hinge-back tortoise. The most common associated side effect following administration of the higher doses of either of the drugs is excessive salivation.

Efficacy and Safety of Vernonia cinerea for Smoking Cessation: An Open-Label Randomized Controlled Trial.

This study aimed to compare the efficacy and safety of Vernonia cinerea (VC) and nortriptyline for smoking cessation. A randomized, active-comparator, open-label trial was conducted in 2019. A total of 84 patients participated in the study, and equally randomized with 42 participants in each group. Overall, there was no statistically significant difference of continuous abstinence rate (CAR) between VC and nortriptyline group (Odd ratio 0.68, 95%CI 0.25-1.85, P=0.451). After week 12, the end of treatment, CAR between both groups was not different (44.44% vs 45.95%, Odd ratio 0.77, 95%CI 0.23-2.54, P>0.999). After follow up by the end of research at week 24, the CAR in both groups was not different (41.67% vs 43.24%, Odd ratio 0.76, 95%CI 0.23-2.55, P>0.999). After week 24, relapse rate between VC and nortriptyline group was not different (13.89% vs 10.81%, P=0.923). In addition, both groups were effective in reducing the number of cigarettes per day compared to baseline. However, there was no difference between the groups. Overall, the VC group had an 8% smoking rate less than nortriptyline group, but not statistically significant (IRR 0.92, 95%CI 0.59-1.43, P=0.702). They also resulted in reducing the exhaled CO level at treatment period and wash out period (at week 12; 7(-17-20) vs 7(-12-16), mean difference 0.78, 95%CI -3.07-4.63, P>0.999, at week 24; 8(-5-22) vs 8.5(-5-17), mean difference 0.39, 95%CI -3.46-4.24, P>0.999). Overall, there was no difference between either group (mean difference -0.31, 95%CI -3.10-2.47). For safety data, adverse events including tongue bitter taste or numbness were found in VC group to be greater than in nortriptyline group (61.9% vs 30.95%, P=0.004), whereas dry mouth and drowsiness were greater found in nortriptyline group (35.71% vs 90.48%, P<0.001 and 16.67% vs 90.48%, P<0.001, respectively). Serious adverse events were not found. In smoking cessation, efficacy and safety of either VC or nortriptyline showed no difference.

Comparing the efficacy of duloxetine and nortriptyline in alleviating the symptoms of functional dyspepsia - a randomized clinical trial.

Aim: To compare the efficacy of Duloxetine and Nortriptyline in alleviating the symptoms of severity, anxiety, depression and quality of life in patients with functional dyspepsia (FD). Material and method: We conducted a single-blinded 3-month trial of Duloxetine 20-30 mg daily in 20 patients and Nortriptyline 25 mg daily in 25 FD patients. The primary outcome measure was the severity of FD symptoms by Gastrointestinal symptoms rating scale. Secondary measures included Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and Nepean Dyspepsia Index. the patients were measured in 3 stages. Results: 45 patients with FD with a mean age of 37.18 ± 10.62 years participated in the study. The severity of symptoms was significantly lower in the Nortriptyline group than in the Duloxetine group after three months (p = 0.031). The level of anxiety (p = 0.049), depression (p = 0.045) and quality of life (p = 0.046) improved significantly after three months in the Duloxetine group compared to Nortriptyline. Mediation analysis using linear regression revealed a significant mediator role for anxiety. This mediation analysis revealed a 21.13% reduction in anxiety in the Duloxetine group. Conclusion: While both medications demonstrated efficacy, Nortriptyline appeared to be superior in symptom reduction. Duloxetine exhibited more advantages compared to Nortriptyline in addressing anxiety and depression and enhancing the overall quality of life. Also, Duloxetine may have a noteworthy impact, contributing to a 20% reduction in FD symptoms by lowering anxiety levels. Clinical trial registration: https://en.irct.ir/trial/65512.

Antidepressants Trial in Parkinson's Disease (ADepT-PD): protocol for a randomised placebo-controlled trial on the effectiveness of escitalopram and nortriptyline on depressive symptoms in Parkinson's disease.

BACKGROUND: Depressive symptoms are common in patients with Parkinson's disease and depression is a significant predictor of functional impairment, reduced quality of life and general well-being in Parkinson's disease. Despite the high prevalence of depression, evidence on the effectiveness and tolerability of antidepressants in this population is limited. The primary aim of this trial is to establish the clinical and cost effectiveness of escitalopram and nortriptyline for the treatment of depression in Parkinson's disease. METHODS: This is a multi-centre, double-blind, randomised placebo-controlled trial in 408 people with Parkinson's disease with subsyndromal depression, major depressive disorder or persistent depressive disorder and a Beck Depression Inventory-II (BDI-II) score of 14 or above. Participants will be randomised into one of three groups, receiving either escitalopram, nortriptyline or placebo for 12 months. Trial participation is face-to-face, hybrid or remote. The primary outcome measure is the BDI-II score following 8 weeks of treatment. Secondary outcomes will be collected at baseline, 8, 26 and 52 weeks and following withdrawal, including severity of anxiety and depression scores as well as Parkinson's disease motor severity, and ratings of non-motor symptoms, cognitive function, health-related quality of life, levodopa-equivalence dose, changes in medication, overall clinical effectiveness, capability, health and social care resource use, carer health-related quality of life, adverse effects and number of dropouts. DISCUSSION: This trial aims to determine the effectiveness of escitalopram and nortriptyline for reducing depressive symptoms in Parkinson's disease over 8 weeks, to provide information on the effect of these medications on anxiety and other non-motor symptoms in PD and on impact on patients and caregivers, and to examine their effect on change in motor severity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03652870 Date of registration - 29th August 2018.