pulmonary arterial hypertension ( pah ) is a debilitating lung disease characterized by persistent elevation of pressure in the pulmonary arteries and pulmonary vascular resistance leading to right heart failure resulting in a progressive decline in the level of functioning . patients present with increased shortness of breath on exertion , palpitations , and fatigue , making it difficult to differentiate these symptoms from other cardiopulmonary diseases . medical research in the past three decades has changed management approach to this disease and today medical therapies such as prostanoids , phosphodiesterase type-5 inhibitors ( pde-5 ) and endothelin receptor antagonists ( eras ) are available to improve exercise tolerance . these medications have reduced mortality and improved exercise capacity and pulmonary hemodynamic parameters . despite these innovations , it is recognized that the debilitating natural history of pah provides a significant challenge for patients and physicians . the aim of this article is to review the current literature of depression in pah . depression is a serious illness characterized by an intense feeling of sadness associated with emotional and behavioral changes affecting anyone regardless of age , race , gender , or socioeconomic status . patients can feel ( a ) hopelessness b ) helplessness ( c ) worthlessness ( d ) agitated ( e ) fatigue ( f ) lack of interest ( g ) decreased concentration ( h ) suicidal thoughts , and ( i ) appetite changes . a clinical diagnosis of depression requires patients to have five or more of the nine symptoms in a 2-week period . these symptoms have a significant effect on the patient 's level of functioning and as a result , interfere with daily activities . depression may be difficult to detect because of lack of specific laboratory parameters pointing toward it . in clinical practice , depression can also be sometimes difficult to diagnosis because of the overlap of symptoms between depression and medical conditions . even when patients meet the criteria of depression , the stigma and misconceptions associated with it can make them skeptic about openly seeking help or having an open discussion with health care providers . once a diagnosis of pah is confirmed , patients have to cope with mixed emotions of understanding and accepting the reality in conjunction with adjustment to their condition [ figure 1 ] . the complex nature of pah , an uncertain future , and a lack of cure can impel feelings of being overwhelmed and the inability to maintain regular social activities . as a result , patients report restrictions in their ability to perform daily tasks such as working , traveling , shopping , and household chores . a recent international survey of pah patients found them to have feeling of worthlessness ( 22% ) , frustration ( 35% ) , anger ( 24% ) , and little pleasure in activities ( 25% ) that they enjoyed prior to pah diagnosis . as patients struggle to cope with an unfamiliar condition , they are frustrated in keeping up with their doctor 's appointment , magnitude of multiple tests , and expenses associated with pah management . additionally , poor sleep quality is common among these patients and it is related to dyspnea , depression , and quality of life ( qol ) . this insurmountable burden can serve as a medium for self - doubt and noncompliance with medication , which in effect raises health care costs . major studies of pah and depression relationship between pulmonary artery hypertension and depression shafazand et al . conducted a study that used nottingham health profile ( nhp ) , congestive heart failure questionnaire ( chq ) , with hospital anxiety and depression scale ( hads ) as a component to access overall health - related qol in pah patients . a total of 53 patients [ mainly new york heart association ( nyha ) functional class iii and iv ] were included in the study and were divided into treatment ( 53% on epoprostenol therapy ) and no treatment ( 47% no epoprostenol therapy ) groups . the patient group not on therapy had significantly more anxiety and depression as compared to the medication group . on average , pah patients reported moderate to severe degree of impairment in all domains of the qol such as social isolation and emotional reaction . participants were so unhappy with their lifestyles that ( 29% ) were prepared to take a risk of death in order to be free of the symptoms of pah . investigated the prevalence of anxiety and depression in pulmonary hypertension ( ph ) patients . in this study , 164 patients were matched in two comparison groups , inflammatory rheumatic diseases ( irds ) and primary care ( pc ) patients , who completed a standardized , validated and self - administered patient health questionnaire ( phq ) . the study found that patients with ph were diagnosed with one or more mental disorders such as anxiety and depression more commonly compared to ird and pc patients . there was also evidence that in pah patients , as the functional class declined , the frequency of mental disorders increased from ( 17.7% ) in nyha ( class i ) to ( 61.9% ) in nyha ( class iv ) . thus , there was also a strong association between increasing functional impairment and mental disorders . looper et al . investigated depressive symptoms and its association with the physical symptoms of ph . fifty - two patients , both precapillary and postcapillary ph patients , who were included in this trial completed the beck depression inventory ( bdi ) questionnaire for depression and it was found that physical functioning was significantly associated with depressive symptoms . moderate to severe depression significantly worsened physical function scores in comparison to minimal or no depressive symptoms . bdi questionnaire was used in 46 patients and it was found that 26% of the patients had some symptoms of moderate to severe depression . mccollister et al . studied the prevalence of depression in a pah as a primary endpoint , using phq-8 . a total of 100 patients were enrolled in the trial and at two separate outpatient visits , the questionnaires were completed and functional class assessment and 6-min walk distance ( 6mwd ) were performed . a high prevalence of depressive symptoms ( 55% ) was found in this study population but only 25% of the patients were taking any type of antidepressant medication . demonstrated that moderate to severe depression was significantly corelated with a lower qol but not with long - term survival . this prospective study of 158 patients with pah and chronic thromboembolic pulmonary hypertension ( cteph ) patients used phq-9 and generalized anxiety questionnaire-7 ( gad-7 ) for assessment . patients with a high gad-7 value also had a high phq-9 value , thus suggesting a significant correlation between the severity of anxiety and depression disorders . in addition , 57.6% of the patients with moderate to severe mental disorder had significant impairment in their daily activities , as compared to patients with no or mild depression ( 11.7% ) . among the patients , 22.8% presented with moderate to severe anxiety or depression and out of them a recent cross - sectional survey was performed to examine the corelation of depression , anxiety , and its effects on 6mwd and health - related quality of life ( hrqol ) in ph patients . conducted a survey of 166 patients by completing depression anxiety stress scale ( dass ) and the dartmouth cooperative functional assessment charts . the findings of this survey were indicative of a link between stress anxiety and qol with ph . screening for depression in the pah population remains challenging because depressive symptoms such as low energy or fatigue can be viewed as part of the underlying disease process . a lack of proper training skills in treating physicians may also play a role in not detecting underlying depression . recently , the us preventive services task force has recommended health care providers to screen and provide effective treatment for depression in adult patients . one method of screening for depression is to utilize questionnaires that have been developed over the years . some of the screening tools available are zung self - rating depression scale , center for epidemiologic studies - depression scale ( ces - d ) , phq-9 , and bdi . these scales are simple to complete and can be done while patients are waiting in doctors offices to be seen by a physician . patients suspected of depression , based on the screening questionnaires , should therefore , undergo a thorough assessment to determine the presence or severity of depression . as patients are being assessed for depression , risk of suicide however , the exact pharmacotherapy for treatment for a pah patient needs to be well - defined . there is limited and contentious data on the use of certain antidepressants such as selective serotonin reuptake inhibitors ( ssris ) for pah patients . performed a retrospective study of 84 patients , out of which 13 patients were taking ssris . the study observed that pah patients had a lower risk of death ( 50% ) compared to those not treated with ssri . pah patients taking ssri were at high risk of mortality and clinical worsening than patients not taking ssris . examined the association between high morbid pregnancy and antidepressant medication usage leading to the development of persistent pulmonary hypertension of the newborn ( pphn ) . the finding of this large cohort suggests that ssri exposure in late pregnancy is associated with increased risk of pphn ; however , the risk was found to be smaller than what was previously proposed . pah patients are already on multiple medications and it conceivably raises the possibility of assessing a nonpharmacological outlook for the treatment of depression . as part of an integrative approach to depression , guidelines are available to efficiently treat it with medication and psychotherapy . current guidelines for depression in the general population recommend the usage of a combination of medication and psychotherapy for moderate to severe depression while psychotherapy along with this can be a valuable first step for mild depression . psychotherapy is an effective form of treatment for depression that allows patients to converse with a health care professional . it is a method that helps patients to understand their behavior that might have contributed to depression . the basic principal of cbt is a focused , structured collaborative environment to assist patients in solving problems and dysfunctional thinking . it is a collaborative effort between patients and clinicians to apply valuable strategies that can help patients to gain control . in addition to behavioral therapy , support groups can also be considered as part of a new innovative option for patients . support groups are voluntary gatherings of patients and their family members that allow them to share their personal experiences with other patients . it is an opportunity to simultaneously provide and receive support , build acquaintances , and share coping strategies . a well - functioning support system can empower patients to manage their condition more wholeheartedly . support groups can have a positive impact on the motivation , confidence , and general well - being of the patient . flattery et al . illustrated that patients actively seek support groups as a way of learning about the disease and methods to cope with the uncertainty associated with it . more recently , pulmonary rehabilitation ( pr ) has emerged as an important and integral part of clinical management of chronic respiratory diseases . there is evidence that pr improves function , disease symptoms , fatigue , and qol in copd and chf patients . pr has been commonly used as a part of standard of care in copd and chf patients . our own data support the perception of improvement in fatigue in advance lung disease after the completion of a pr program . found in a cohort of 21 patients a significant improvement in fatigue and suggested an improvement in depression symptoms after completing pr . there is an increasing thought process that pulmonary exercise may be beneficial in these patients and clinical data are suggestive of the usage of pr in improving depression . mereles et al . evaluated the effects of daily exercise in a 15-week trial of 36 patients . at the end of 15 weeks of pr exercise training was associated with significant improvement in the qol as measured by sf-36 questionnaire . saglam et al . recruited 29 stable pah patients who were either in a inspiratory muscle training ( imt ) group or a control group for 6 weeks and their qol was assessed by nottingham health profile ( nhp ) . after completion of pr , patients in the imt group had considerable improvement in muscle strength as well as emotional and psychosocial dynamics . another contemporary approach as an adjunctive therapy for anxiety and depression is progressive muscle relaxation ( pmr ) techniques , pmr is technique developed to relax various body muscles in order to manage anxiety and stress . recruited 130 pah patients who were randomized to be either the control group or treatment group for 12 weeks . in comparison to the controls , the study found that patients in the treatment arm had significant improvement in depression and overall qol . this coexistence of pah and depression presents health care workers with a challenge but also an opportunity . it is a challenge because of lack of appropriate guidelines for confronting depression with pah and therefore , leaving its treatment to the clinical judgment of physicians and patient preference . limited studies have highlighted its significance ; the exact association has not been fully addressed . unfortunately , large scale clinical trials at times may not be possible because of competing illnesses , limited resources , and infrastructure . in such cases , conducting observational studies is beneficial in identifying pah patients with depression . it is also the right opportunity for health professionals to focus on a ) obstacles in diagnosing depression , b ) addressing obstacles in treating depression , and c ) clarifying the ideology of using depression as an outcome measure and its relationship to 6mwd , if any . with this approach , perhaps health care policy - makers can also create methodical guidelines in approaching depression and helping physicians in avoiding a medical conundrum of whether or not to use medications . finally , to address the fundamental shortcomings of health care delivery , an efficient and effective chronic care model should be created for pah patients , as similar models have shown evidence of improved care for congestive heart failure , diabetes mellitus , and asthma . six keys elements have been identified in the chronic care model : health system redesign , decision support , information systems , community involvement , organization , and self - management support for empowering patients [ table 2 ] . by developing a chronic care model for pah patients , it will propel physicians toward the establishment of a patient - centered outcome approach . outcome approach can empower physicians to embrace web portal - like electronic medical records ( emrs ) by allowing effective , efficient , and accurate communication with other team members in patient care . simple tools embedded in emrs such as medication dosing or side - effect profile can be helpful in decision - making . moreover , health portal websites have enabled patients to be more informative about their condition and empower them as well to share responsibility in the management . these simple measures can ensure that patients get optimal care and hence , bring an overall improvement in the treatment outcome . accordingly , it is possible to detect depression early by using screening questionnaires and treat it without delay . this may help in reducing distress , improving daily functioning , and leaning toward living a better qol . while there is a paucity of data about the psychopharmacological agents for pah patients for that reason , more qualitative research is needed to precisely define their roles in pah management .
pulmonary arterial hypertension ( pah ) is a debilitating condition leading to progressive decline in functional capacity . as a result 
 , pah can lead to psychological impairment that can impact the overall disease status . 
 the medical community has developed several screening questionnaires in order to assess depression in their patients allowing physicians to be at the forefront of recognizing clinical depression . 
 there is a suggestion that depression symptomatology is more prevalent in the pah population . 
 the aim of this article is to review the current thought process about diagnosis and management of depression in pah patients .