Management of Psychiatric Disorders in Patients with Respiratory Diseases.

INTRODUCTION

The respiratory diseases can be broadly classified into obstructive, restrictive, infective, and other groups as shown in Figure 1 which will be addressed in this guideline. This chapter will also incorporate the respiratory adverse effects of various psychotropic drugs with special mentions about smoking cessation, obstructive sleep apnea (OSA), and management of COVID-related respiratory diseases.[1]

Figure 1

Classification of respiratory diseases

The various considerations of managing psychiatric disorders in patients of respiratory diseases can be summarized in broad headings, for example, in acute or critical care settings, substance use disorders with respiratory diseases, chronic care settings, psychiatric disorders in chronic respiratory diseases, COVID, and psychiatry especially the neuropsychiatric manifestations of COVID, management of OSA with psychiatric comorbidities, management of psychogenic dyspnea (hyperventilation syndrome), and pharmacological adverse effects of psychotropic medicines. Common mental disorders such as depression and anxiety increase the morbidity and mortality of the patients with respiratory illnesses. Nevertheless, severe mental disorders evidently complicate the scenario. The management protocol demands a thorough knowledge of pathophysiology, subtle nuances of general and psychopharmacology, along with a clinical knowledge knitted with soft skills. For convenience, broadly, we classified our chapter into clinical conditions in acute and chronic care settings and then tried to discuss the management of psychiatric issues of the primary respiratory diagnoses. The general approach and the key features are summarized in tables or flow charts.

ACUTE CARE SETTING

The common scenario in acute care settings is delirium where a psychiatrist is frequently called for. Readers are referred to IPS guideline on delirium for the details. In respiratory care settings careful assessment of the respiratory system medications, history of recent substance abuse/intoxication or withdrawal, finding the actual medical cause of the acute behavioral disturbance (ABD) state, choosing appropriate medication to manage the situation is the critical tasks for a psychiatrist. The general principle of psychotropics use is highlighted in Table 1 and Flowchart 1 describes the management of drug-induced ABDs.[23]

Table 1

General principles for psychotropics used in delirium

Polypharmacy discouraged

The benzodiazepines and antipsychotic drugs should be used judiciously and at a lowest possible dose for a shortest period of time

Titrate for optimum, not maximum; discontinue as clinical picture improves

Doses need to be tailored according to age, weight and most importantly degree of agitation

Small frequent doses are preferred over longer and larger doses

Review at least every 24 h

If ‘as needed’ doses are required frequently, scheduled doses should be optimised accordingly

Clear plan of weaning to be documented if discontinuation is not possible in acute care settings

Flowchart 1

Medication-induced acute behavioral disturbance in emergency admissions

SUBSTANCE USE DISORDER AND PULMONARY DISEASES

Managing “dual diagnosis” (major psychiatric disorder along with substance use disorder) is always challenging. It becomes more challenging with the presence of triple diagnosis, i.e., along with this the presence of medical comorbidities. The street and nonprescribed drugs may lead to many adverse health consequences including different thoracic complications. In case of the dependent pattern of use, the respiratory system has an inner defense to combat from exposure of toxin and substance-related injury to lung parenchyma which is evident in chronic pulmonary diseases. The damage of lung parenchyma caused by tobacco is mostly slow but progressive. Cigarettes/bidi contains hundreds of toxic compounds including carcinogens. Quitting smoking at any time, at any stage of life or disease is beneficial. The proper tobacco cessation program must have to be planned accordingly. Although cannabis is less associated with cancers, however bronchitis, emphysema, increased risk of pulmonary infections are also very common. As a stimulant drug, cocaine is associated pulmonary hypertension, vasoconstriction, and coronary artery diseases. Smoking cocaine is associated with “crack-lung” (triad of hemorrhages, pulmonary edema, fluid retention in the lungs) along with increased risk of cancer. Chronic opioid users are at increased risk of hypoxia, exacerbation of OSA, bronchitis, and emphysema, decreased immunity or pulmonary edema. Inhalant abuse may be associated with acute lung injury or even increased propensity to thromboembolic disease.[4] The potential severity of causing lung diseases of various psychoactive substances is described in Table 2. The details of management of such issues are discussed in clinical practice guideline for substance use disorders of the Indian Psychiatric Society.

Table 2

Substance use disorders and pulmonary diseases

Substance	Associated pulmonary disease
Tobacco	High risk factor for causing COPD and bronchogenic carcinoma, detrimental to any pulmonary condition
Cannabis	Lung cancer
	Chest symptoms pointing to COAD
	Allergic bronchopulmonary fungal infections, with aspergillus, mucor, penicillium, and thermophilic actinomycetes. The all have been found in cultured samples of cannabis
Opioids	Inhibits the respiratory drive
	May lead to death due to respiratory failure
	Aspiration pneumonia, ARDS with sepsis
	ICU admission with oxycodone and hydrocodone overdose are common and the most commonly co-ingested substances are benzodiazepine and methamphetamines
	Increased association with treatment resistant tuberculosis
Alcohol	Increase susceptibility to lung infections and injury
	Increased risk of developing ARDS
Methamphetamine and cocaine	Idiopathic PAH
	Crack lung which is an acute pulmonary syndrome develops up to 48 hours after cocaine inhalation, evident with radiologic changes of alveolitis and histologic findings of diffuse alveolar damage and hyaline membranes
	Spontaneous pneumothorax, pneumomediastinum, bronchitis, pneumonitis, and bronchospasm (when smoked)
Inhalant nitrous oxide	Increased level of methyl malonyl-CoA and homocysteine. Increased homocysteine is a risk factor for venous thromboembolism, which can present with pulmonary embolism as a medical emergency

COAD – Chronic obstructive airway disease; ARDS – Acute respiratory distress syndrome; ICU – Intensive care unit; COPD – Chronic obstructive pulmonary disease; PAH – Pulmonary arterial hypertension

BRIEF INTERVENTION FOR SMOKING CESSATION

This kind of short-term interventions is helpful to generate awareness, share knowledge and make changes to improve health and avoid undesired behaviors. It makes the most of any opportunity to raise awareness, share knowledge and get someone to think about making changes to improve their health and behaviors. It has been effectively used in the treatment of addictive disorders. Brief intervention includes motivational interviewing and goal setting. It takes around 3 min to complete the session. The five a’s for smoking cessation is a global framework used in brief intervention which was very popular, effective in encouraging and providing support to smoking cessation attempts.[5] One can refer to the Indian Psychiatric Society’s Guidelines on substance use disorders for detailed information.

Five a’s of brief intervention are as follows:

Ask or enquire from the patients whether they smoke

Advise and encourage the tobacco users to quit

Assess their motivation levels to quit

Assist and support them in their quitting attempt

Arrange for follow-up.

CHRONIC CARE SETTING

Psychiatric disorders in chronic respiratory diseases

Chronic respiratory diseases or CRD involves lung parenchyma and among them chronic obstructive airway diseases, bronchial asthma, occupational lung diseases (OLDs), and pulmonary hypertension are common. It has been seen that a major percentage of patient with chronic obstructive pulmonary disease (COPD) suffers from psychiatric issues, depression, and anxiety being most common. In addition, the prevalence of depression and anxiety is almost six times more in asthma patients than in general population. We will discuss the management of the psychiatric disorder in COPD and asthma here.

Chronic obstructive pulmonary diseases

There are global initiatives for chronic obstructive lung disease which has termed COPD as a disease which is characterized by limitation of airflow, partially reversible presenting as breathlessness, and other relevant systemic findings. In contrast to asthma, the limitation of airflow in COPD is almost irreversible and usually, it worsens as time proceeds. One of the main causes attributed to COPD is smoking, which is well prevalent in patients with psychiatric disorders.

Over the years, COPD has been attributed to mortality and morbidity globally. Studies show that anxiety and depression are very much comorbid with COPD in both young and old patients. The spectrum of comorbidity ranges from significant symptoms to full diagnosis of mental disorders as per DSM or ICD. It has been seen that anxiety and depression in COPD are often present together as a comorbid condition. The common presentations of anxiety and depression in COPD are as follows:

Fatigue

Weight changes

Sleep disturbances

Agitation

Irritability

Difficulty in concentration.

The cognitive symptoms are also very much prevalent among the patients suffering from COPD. Other studies demonstrate a high prevalence of cognitive dysfunction in patients with COPD. The cognitive dysfunction is specifically seen as dysfunction in verbal skills and verbal memory but often there is preserved verbal attention. The classification of anxiety, cognitive, and mood disorders in patients suffering from COPD is summarized in Table 3.6]

Table 3

Classification of disorders of cognitive, mood and anxiety in patients suffering from chronic obstructive pulmonary disease

Cognitive disorders	Mood disorders	Anxiety disorders
Delirium	Major depressive disorder	Generalized anxiety disorders
Dementia	Bipolar disorder	Panic disorder
Amnesia	Dysthymia	Social anxiety disorder
Mild cognitive impairment		PTSD
		Specific phobia

PTSD – Posttraumatic stress disorder

Treatment of cognitive disorders in COPD

Improved cognition in COPD patients has shown to decrease the disease outcome such as acute exacerbations, hospitalization rate, and improve quality of life. Oxygen therapy is found to be efficacious in case of cognitive disorders in COPD as it improves the cerebral blood flow. Researchers have found that continuous oxygen therapy provides a better outcome than nocturnal oxygen therapy trial in reducing mortality rate.

Pulmonary rehabilitation has been processed for chronic respiratory impairments. It improves the cognitive function since poor performance in aerobic fitness is a potential risk factor for cognitive decline. It is an individualized program delivered to the patient and the family by the therapist. Details are discussed afterward.

Regarding pharmacological therapy, limited data exist. Formoterol, a beta 2 agonist used to treat COPD has shown some efficacy in improving density in synapse as well as cognitive function. Roflumilast, a PDE-4 inhibitor has also shown some improvement in cognitive functions in COPD patients. For patients with delirium, low-dose haloperidol or any other second-generation antipsychotics can be used depending on the patient profile. The management of comorbid psychiatric issues is necessary. The role of cognitive enhancers is doubtful. The assessment of cognitive dysfunction [Flowchart 2], management of mild and moderate cognitive dysfunction [Table 4] and management of severe cognitive dysfunction [Flowchart 3] have been summarized below.[7]

Flowchart 2

Assessment of cognitive dysfunctions in COPD

Table 4

Treatment of mild/moderate cognitive disorders in patients suffering from chronic obstructive pulmonary disease

Oxygen therapy: Oxygen therapy continuously provides better outcome than NOTT. It improves cognitive function in long term, slows cognitive decline, decreases mortality. It also improves cerebral blood flow

Pulmonary rehabilitation: Improves exercise capacity, improves cognition

Pharmacotherapy: Mostly used in secondary psychiatric issues. Sedatives, if used, should be of less duration to slow cognitive impairment. No definite role of cognitive enhancer

NOTT – Nocturnal oxygen therapy trial

Flowchart 3

Treatment of severe cognitive decline in patients suffering from COPD

Pulmonary rehabilitation

Pulmonary rehabilitation or respiratory rehabilitation is an integral and crucial part of management in patients suffering from COPD, who continue to remain symptomatic despite standard medical treatment. The aim of the rehabilitation is to improve general sense of well-being and quality of life of the patient and their caregivers. The main component of the rehabilitation is the supervised pulmonary exercises, which helps in addressing the issues such as limitation of ventilator efforts, limitation of gas exchanges, coronary, respiratory, and skeletal muscle dysfunctions. The other components include smoking cessation, emotional support, and nutritional support to improve the quality of life of the patient in general.[8] The indications and components of pulmonary rehabilitations are summarized in Table 5a and b.

Table 5a

Indications of pulmonary rehabilitation

Obstructive disorders

COPD

Persistent asthma

Bronchiectasis

Restrictive disorders

Interstitial fibrosis

Sarcoidosis

Kyphoscoliosis

Parkinson’s disease

Lung cancer

Pulmonary hypertension

After lung transplant

Before and after lung surgery

COPD – Chronic obstructive pulmonary disease

Table 5b

Components of pulmonary rehabilitation

Exercise training

Inspiratory muscle training

Neuromuscular electrical stimulation

Facilitate smoking cessation

Optimize pharmacotherapy

Detect and manage acute exacerbations

Manage acute dyspnea

Increase physical activity

Nutritional evaluation

Promote mental health

Advanced care planning

Treatment of anxiety and depressive disorders with chronic obstructive pulmonary disease

The treatment of depressive and anxiety disorders in patients suffering from COPD involves both pharmacotherapy and psychotherapy. For mild-to-moderate depressive disorder, the first line of treatment is psychotherapy. Several modes of psychotherapy can be done depending on the patient’s needs. Cognitive behavioral therapy, group psychotherapy, interpersonal therapies are the few options. For moderate-to-severe depressive or anxiety disorders, pharmacotherapy is the first line of drug.

SSRIs are the first choice as antidepressants. Alternatively, SNRIs can be used. Drugs should be used judiciously and half-life, drug-drug interactions should be kept in mind. Precautions should be taken while using fluoxetine, as it has a longer half-life. Fluoxetine, fluvoxamine, and paroxetine are CYP3A4 inhibitors, should be used cautiously with COPD drugs. Tricyclic antidepressant (TCA) should better be avoided, as anticholinergic side effects are more prominent in elderly persons, can cause sedation too. Noradrenergic and specific serotonergic antidepressants (NaSSA)/Norepinephrine and dopamine reuptake inhibitors (NDRI) can be used as second line of drug. Benzodiazepines should be used in low dose and for minimum duration. Augmentation can be done with second-generation antipsychotics or mood stabilizers depending on the patient profile. Lithium should be used very cautiously as COPD patients are already prone to dyselectrolytemias.[9] Other treatment options in addition to pharmacotherapy involve psychotherapy and pulmonary rehabilitation. The management approach is described in Flowchart 4.

Flowchart 4

Management of depression and anxiety disorders in COPD

Bronchial asthma

Asthma is a common chronic respiratory disorder that involves inflammation of airway. During acute exacerbations, the patient complains of shortness of breath, chest tightness, coughing, and wheezing. Bronchial asthma is usually treated by rescue inhalers like Salbutamol to treat symptoms and controller inhalers like steroids to prevent exacerbation of symptoms. In severe cases, often long-acting inhalers like salmeterol, formoterol, tiotropium as well as inhalant steroids help to keep the airways open.

In epidemiological studies, it has been commonly found that anxiety, depressive, substance use disorders, suicide, and schizophrenia carries a high probability of being comorbid with Bronchial asthma. During acute exacerbations, patients with asthma face anxiety, panic, irritability, frustrations closely resembling psychiatric symptomatology. The experience of the respiratory disease may lead to secondary psychiatric problem. Similarly, psychopathology may result in alteration of immunological/inflammatory pathway involved in asthma. Thus, asthma symptoms present in childhood often presents with anxiety disorder in adulthood. Elevated levels of a range of psychiatric conditions are found in the first-degree relatives of asthma patients. This also explains the genetic basis.

Existing psychiatric disorder and asthma can influence each other in various ways. Overlap of symptoms can cause challenges in the management of both asthma and psychiatric disorders. Prominent positive symptoms of schizophrenia can distract physicians from comorbid asthma and lead to underdiagnosis and undertreatment. Similarly, patients with panic disorder with comorbid asthma seem to have higher rates of hospitalization and emergency room visit due to “panic-fear” [Flowchart 5]. Strong emotional states associated with psychopathology may affect asthma directly mainly through parasympathetic excitation, hyperpnea, and hypocapnia. Psychiatric patients with altered mood can also affect disease management of asthma, for example, over or inadequate use of rescue inhalers, poor adherence to treatment protocols, neglect of trigger control, problem behavior like smoking, delayed treatment seeking. Symptoms of asthma can be an origin to panic and lead to fatigue and exhaustion experienced in psychiatric disorders. Internalizing disorders in children seeking cognitive behavior treatment are more serious in those comorbid with asthma.[10]

Flowchart 5

Apprehension and anxiety about relapse of asthma

Bronchial asthma is also has a higher risk to be associated with cognitive disorders like mild cognitive impairment, and diagnosis of asthma in early life increases the chance of development of dementia in later life. The association between asthma and cognitive disorders is not known but could be related to reduction in respiratory functions, inflammatory processes. Medication treatment for both asthma and psychiatric disorders has an adverse effect. High doses of benzodiazepines and hypnotics can lead to respiratory depression. SSRIs are the mainstay of pharmacotherapy for anxiety and depression. For treatment guideline, the same can be followed as in COPD.

Use of propranolol in patients with asthma

Propranolol is a peripherally acting nonselective beta-blocker, advised to treat patients suffering from anxiety disorders especially performance anxiety disorder and essential tremor. It is absolutely contraindicated in COPD due to robust evidence of exacerbation of pulmonary symptoms. Its role in patients with asthma is debatable. Although previously considered unsafe; current literature support favors its use in low doses with a gradual escalation of dose in mild-to-moderate asthma. Current literature is against its discontinuation in asthma if there is associated systolic heart failure, as it has a definite survival advantage. Cardio-selective beta-blockers such as Atenolol, Bisoprolol, Metoprolol are better options if risk of asthma exacerbation is considered. Although after initial doses, there is ≥20% reduction of forced expiratory volume in asthmatics; their apparent risk is short lived and ameliorated in chronic uses.

Adjunctive cognitive and behavioral treatment modalities for asthma

These are treatment modalities that have been adapted for asthma, not directed towards treating comorbid psychiatric conditions but to reach the psychologically relevant deficits in patients with asthma, such as maladaptive breathing patterns, inaccurate perception of airway obstruction, or suffering from excessive stress.[11]

Training of breathing pattern

Certain breathing patterns can hyperpnea or hypocapnia and increase asthma symptoms. These are replaced by more slow, abdominal, shallow, more regular, and or nasal breathing by training modalities. This can induce a better gas exchange efficiency. Feedback can also be provided to increase respiratory sinus arrhythmia, which has been associated with similar benefits.

Interoception training

This can address a potentially dangerous lack of awareness of airway obstruction in patients with asthma. It is often administered to make the patient understand the different loads or to lower their perceptual thresholds for just noticeable load.

Others

Various forms of yoga, meditation, relaxation exercises are administered to decrease the distress associated with asthma.

LUNG CANCER

Bronchogenic carcinoma attributes to almost 20% of all deaths due to malignancy. The use of tobacco has been proved as a direct risk factor whereas secondhand or passive smoking, occupational exposure of asbestos, silica, radon, and other carcinogens also contribute directly or indirectly in causation of lung cancers. The major limitations for having poor 5-year survival rate are lack of awareness and early detection. The commonest histological diagnosis is non-small cell lung carcinoma (NSCLC) followed by SCLC.

Higher emotional distress is faced by the patients suffering from lung cancer in comparison to other cancers. The distress remains throughout the disease course, from diagnosis to treatment proper. The common psychiatric disorders that are encountered in lung cancer patients are depressive and anxiety disorders, stress- and trauma-related disorders, cognitive impairment. Less common are bipolar disorders and psychosis.

Anxiety disorders

Anxiety is the most common presentation after diagnosis of cancer. Anxiety may present as an acute reaction to the diagnosis, or recurrence or treatment failure. It may be associated with depressive symptoms, lack of appetite, and decreased sleep. The patients having premorbid anxiety issues may suffer more.

The treatment of anxiety disorders in lung cancer involves both pharmacological and nonpharmacological treatment. Pharmacological treatment includes antidepressants, antipsychotics, and benzodiazepines. Drug choice should be made keeping the patient’s medical illness in mind. Nonpharmacological treatment includes cognitive-behavioral therapy (CBT), psychoeducation, meaning-centered psychotherapy (MCP), and supportive psychotherapy.

Depressive disorders

Depression is a common psychiatric comorbidity in case of lung cancer and also a risk factor for suicide. The patients are at higher risk of suffering from depression in every stage of cancer. Identifying the early signs of depression and thus leading to early treatment, can improve the quality of life (QOL), better treatment adherence, less drop-outs and decrease the risk of suicide.[12]

The risk factors for depression and medical causes of depression are summarized in Table 6a and b, respectively.

Table 6a

Risk factors for depression in lung cancer patients

Old age

Advanced disease stage

Secondary to organ failure or from nutritional, endocrine, neurological complications of cancer

Presence of other co-morbid medical illness

Previous history of depression

Family history of depression

Uncontrolled pain

Low socioeconomic support

Social isolation

Significant loss

Drugs

Table 6b

Medical causes of depression in lung cancer patients

CNS metastasis

Paraneoplastic syndrome (mainly SCLC)

Electrolyte disturbances

Systemic disorders like

Autoimmune disorders

Inflammatory disorders

Infections

Endocrine abnormalities

Hypothyroidism

Adrenal insufficiency

Drugs

Chemotherapeutic agents

Steroids

CNS – Central nervous system; SCLC – Small cell lung carcinoma

The management of depressive disorders in lung cancer involves a comprehensive approach. A therapeutic alliance and recruiting family support are necessary before proceeding. A complete assessment and evaluation of medical illness should be done. The treatment of depression should be done along with the cancer treatment, thus relationship with the oncologist or radiotherapist should be maintained. The treatment involves both pharmacological and nonpharmacological strategies.

Pharmacological treatment

The use of antidepressants in a cancer patient is challenging. The treatment warrants quick action, especially in the terminally ill patients, however, the antidepressants take several weeks to act. The choice of anti-depressant should be made keeping in mind the patient’s profile, medical illness, drug-drug interactions.

SSRIs are the first-line drug used in the treatment of depression in cancer patients. They are generally well-tolerated, have less drug-drug interactions, and not so toxic in overdose. SNRIs are a newer class of antidepressants comprising venlafaxine, desvenlafaxine. These drugs are usually well-tolerated and adverse effects are at par with that of SSRIs. However duloxetine (an SNRI), through its effect on norepinephrine monoamine nuerotransmitter may result in palpitation and hypertension. Thus, blood pressure should be monitored regularly. TCAs are relatively older and less expensive than other antidepressants. However, they are better to be avoided in medical ill persons owing to their anti-cholinergic, anti-histaminic, and anti-adrenergic side effects. Bupropion, an NDRI may have a mild stimulant effect owing to its action on dopaminergic system. This may be beneficial to cancer patients, especially having fatigue or psychomotor retardation. However, this should be used judiciously in patients with central nervous system (CNS) metastasis because of risk of seizure disorders. Mirtazapine is also a good choice of anti-depressant in patients diagnosed with bronchogenic carcinoma. Its adverse effects like sedation and weight gain can have therapeutic advantage in patients having been diagnosed to suffer from terminal illnesses like cancer. It also has low drug-drug interactions.

Electroconvulsive therapy

Electroconvulsive therapy (ECT) is an effective therapeutic option especially for severely depressed patients who have not responded to psychopharmacological treatment (at least trial of two antidepressant from different class with adequate dose and adequate time). This can also be an option for patients having high suicide risk, side effect to antidepressant medicines, or cachexic patients. Although it is not an absolute contraindication to CNS metastasis, ECT should be used in these individuals with caution.

Psychotherapy

Several psychotherapeutic techniques are available for the treatment of depressed cancer patients. They are often combined with pharmacological treatments. Supportive psychotherapy and CBT are among the most used psychotherapies. MCP is a novel therapy that has been effective in improving depressive symptoms among advanced cancer patients [Flowchart 6]. Group therapy is also useful.[13]

Flowchart 6

Meaning centered psychotherapy

Suicide in lung cancer

The risk of suicide among lung cancer patients is higher than the general population. Often it is required to diagnose them early and admit them for supervised inpatient care in a mental health institutions (MHI) [Table 7]. Suicidal ideations should be considered from 4 perspectives-

Table 7

Suicide risk factors in patients suffering from lung cancer

Depression

Hopelessness

Uncontrolled pain

Extreme fatigue

Anxiety

Delirium

Substance abuse

Past history of suicide attempt

Family history of suicide

Suicidal thoughts coming transiently and occasionally

Suicidal thoughts coming in patients with good prognosis or remission

Suicidal thoughts coming in patients with poor prognosis

Patients with terminal disease.

The management of depression in patients suffering from bronchogenic carcinoma is very challenging and is summarized in Flowchart 7.

Flowchart 7

Management of depression in cancer patients

Cognitive impairment

Delirium is one of the most serious neuropsychiatric complications encountered in any cancer patient. In case of lung cancer, the percentage of patient having delirium is relatively high [Table 8]. If undertreated, delirium adds to the morbidity and mortality of the cancer patients. It is a medical emergency and should be treated promptly.

Table 8

Causes of delirium in lung cancer patients

Direct cause

CNS metastasis

Indirect cause

Hypoxia

Metabolic encephalopathy

Electrolyte imbalance

Infection

Paraneoplastic syndromes

Treatment side-effects from chemotherapeutic drugs, steroids, opioids, anticholinergics, benzodiazepines

Alcohol or drug withdrawal state

There are different instruments developed and standardized in different vernaculars for assessment of delirium like Delirium Rating Scale (DRS), the Confusion Assessment Method (CAM), the Memorial Delirium Assessment Scale [MDAS]. MDAS is a 10-item scale validated in hospitalized patients with advanced cancer. A cut-off score of 13 is confirmatory to diagnose an individual is suffering from delirium.

Treatment

The treatment approach to the management of delirium includes evaluation and removing the offending cause. Symptomatic management includes both nonpharmacological and pharmacological treatment. Haloperidol is the gold standard in the management of delirium among cancer patients, due to its efficacy and safety profile. Other second-generation antipsychotics can also be used [Table 9]. The management of delirium in lung cancer patients is comprehensively summarized in Flowchart 8.

Table 9

Doses of antipsychotic drugs used in delirium

Drugs	Doses
Haloperidol	0.5-2 mg every 2-12 h
Chlorpromazine	12.5-50 mg every 4-12 h
Olanzapine	2.5-10 mg every 12-24 h
Risperidone	0.25-2 mg every 12-24 h
Quetiapine	12.5-200 mg every 12-24 h
Ziprasidone	10-40 mg every 12-24 h
Aripiprazole	10-30 mg every 24 h

Flowchart 8

Management of delirium in lung cancer patients

Trauma- and stress-related disorders

Trauma- and stressor-related disorders involve acute stress disorders, adjustment disorders, and PTSD. This group of disorder is very common after the diagnosis of any cancer. Getting a diagnosis of cancer is perceived as a life-threatening event. All the three disorders are equally found after a diagnosis of lung cancer. The treatment involves early identification, crisis intervention, relaxation training. A support group may be helpful. Patients with more severe symptoms should be treated with antidepressants and anxiolytics.

Bipolar disorders

Bipolar disorder in the cancer setting must be immediately referred to a psychiatrist owing to the complexity of treatment. The manic or violent patient must be calmed down as soon as possible as treatment of cancer needs a lot of co-operation from the patient side. Lithium should be used judiciously in case of cancer patients given its side effect profile. Lithium should be monitored in lung cancer patients with kidney disorder. SCLC-type lung cancer can cause SIADH as a part of paraneoplastic syndrome. While using Lithium in such patient, occurrence of diabetes insipidus should be kept in mind. Ongoing medication, if the patient is a known case of bipolar disorder should be continued and monitored closely. Close liaison should be maintained with oncologist and radiotherapist.

Schizophrenia and psychosis

Schizophrenia patients with lung cancer may give idiosyncratic meaning to the cancer symptoms and may tolerate them owing to their high pain threshold. Often, they are being diagnosed at a late stage. The ongoing medications should be continued along with the anti-cancer treatment. The side effect profile of the anti-psychotic drugs should be kept in mind.

COVID AND PSYCHIATRIC ISSUES

COVID-19 is a communicable disease caused by severe acute respiratory syndrome coronavirus-2. It has been diagnosed first in Wuhan province of China in November 2019.[14] Since then, it is the reason behind the ongoing global pandemic. It is discussed in detail in a separate chapter. Here, the salient points in general management of COVID and psychiatric illnesses will be discussed very briefly.

General management of psychiatric patients suffering from COVID-19

The general psychiatric management of the COVID patients can be divided into two categories:

Patients already on psychotropic medications who is recently infected with COVID

COVID patients developing newonset psychiatric complaints.

The general management is in Flowcharts 9 and 10.

Flowchart 9

Management of psychiatric patients developing COVID-19

Flowchart 10

Management of persons with mental disorders patients in COVID wards

OBSTRUCTIVE SLEEP APNOEA

Common psychiatric comorbidities of OSA are depression, anxiety along with substance use disorders - tobacco and alcohol predominantly. Certain personality traits, eating disorders predispose to weight gain and indirectly to OSA, however the direct bidirectional relationship of psychiatric disorders and OSA is controversial. Continuous positive airway pressure (CPAP) is the first treatment of choice. Despite its well-recognized benefits including neuropsychological and depressive symptoms, CPAP acceptance and adherence remain problematic. Other alternative nonpharmacological treatments are oral appliances, weight loss, and surgery. Pharmacological agents could be useful adjuncts than main treatment.[15] Readers are advised to go through the clinical practice guideline of the Indian Psychiatric Society on sleep disorders for a detailed discussion of OSA. A general management of OSA with psychiatric comorbidities is summarized in Table 10.

Table 10

Management of obstructive sleep apnoea with psychiatric comorbidities

OSA (points to remember)
Substance use - tobacco, alcohol; anxiety, depression are common comorbidities
Healthy life style, weight loss, CPAP adherence- need to be emphasized
Use of psychotropics should be rational
Atypical antipsychotics cause increased upper airway tone, weight gain
TCA, SSRIs are permissible. Fluoxetine with ondansetron could be beneficial
Short term use of zolpidem is better than benzodiazepines
Avoid long use or larger dose of stimulants
NRT (Nicotine chewing gum) could be a good choice
Topiramate could be a good choice for relapse prevetion
CBT-I may be beneficial

CPAP – Continuous positive airway pressure; TCA – Tricyclic antidepressant; OSA – Obstructive sleep apnoea; SSRI – Selective Serotonin Reuptake Inhibitor; NRT – Nicotine Replacement Therapy; CBT-I – Cognitive Behavioral Therapy for Insomnia

OCCUPATIONAL LUNG DISEASE

The OLDs are increasing with the global industrialization and primarily attributed to occupational exposure to toxic substances in workplace. This group encompasses a broad spectrum of diseases such as COPD, inhalation injury, industrial bronchitis, bronchiolitis obliterans, occupational asthma, interstitial lung diseases (hypersensitivity pneumonitis, pneumoconiosis, lung fibrosis, infections, mesothelioma, and lung cancers).[16] The OLDs can be caused directly or indirectly due to immunological responses to these exposed chemicals, dusts, proteins, or organisms. The prevalence of psychiatric disorders in OLD has not been a favorite topic of research. It has been found that depression and anxiety are real commonly prevalent, related to the severity of dyspnea and should be treated according to the disease. Delirium is also common in a more chronic and severe form of diseases and should be treated accordingly.

HYPERVENTILATION SYNDROME OR PSYCHOGENIC DYSPNOEA

Hyperventilation syndrome or psychogenic dyspnea is a common disorder that presents to the emergency department very often. They may present with sudden onset shortness of breath, chest tightness and pain, dizziness, vertigo, numbness, or near syncope generally after a stressful event. Though before diagnosing, we need to eliminate other medical causes of dyspnea.[17]

The necessary investigations and clinical work-up should be done before proceeding for the treatment of psychogenic dyspnea. Acute coronary syndrome and pulmonary embolism are acute emergencies which need immediate attention. A routine workup including pulse-oximetry, electrocardiography, chest radiography should be done alongside clinical assessment [Flowchart 11].

Flowchart 11

Approach to a patient presenting with hyperventilation syndrome

Some common causes of dyspnea are summarized in Table 11.

Table 11

Some common medical causes of dyspnoea

Anaphylaxis

Acute exacerbation of asthma

Acute exacerbation of COPD

Acute coronary syndrome

Cardiac tamponade

Cardiac failure

Pulmonary embolism

Pneumothorax

Carbon monoxide poisoning

Upper airway obstruction

Broken ribs

Anemia

COPD – Chronic obstructive pulmonary disease

PSYCHOTROPICS CAUSING RESPIRATORY SIDE-EFFECTS

The psychotropics causing respiratory adverse effects are broadly summarized in Table 12.

Table 12

Psychotropics affecting respiratory system

Classification of drugs	Drugs	Respiratory adverse effects
Antidepressants	TCAs	Adult respiratory distress syndrome, pulmonary embolism, pulmonary infiltrate, respiratory depression
	Desvenlafaxine/venlafaxine	Eosinophilic pneumonitis
	Duloxetine	Eosinophilic pneumonitis
	Mirtazapine	Can cause aspiration pneumonia in toxic dose
FGAs	Butyrophenones	Dyspnea, pulmonary embolism, pulmonary vascular disease
	Phenothiazines	Pulmonary embolism
SGAs	Risperidone	Dyspnea, cough
		Rhinitis and upper respiratory tract infection more common in pediatric population
	Quetiapine	Dyspnea, cough, pharyngitis, rhinitis, nasal congestion
	Clozapine	Eosinophilic pneumonitis
		Can cause aspiration pneumonia due to sialorrhea
All FGA sand SGAs can rarely cause acute laryngeal dystonia
Mood stabilizers	Lithium	Very few case reports of pulmonary hypertension
	Valproate	Rarely diffuse alveolar hemorrhage or Interstitial pneumonitis
	Carbamazepine	Cough, dyspnea, pulmonary infiltrate, interstitial pneumonitis, hypersensitivity lung disorder
	Lamotrigine	Rhinitis rarely
Antiepileptics	Phenytoin	Cough, dyspnea, hypersensitivity lung disorder
	Topiramate	Upper respiratory tract infection, when used as monotherapy, 400 mg/day
		Risk of nonanion gap metabolic acidosis, can cause hyperventilation
Acetyl-cholinesterase inhibitors	Donepezil	Can cause exacerbation of COPD rarely
		Rivastigmine
		Galantamine
Sedative-hypnotics	Barbiturates	Dyspnea
	Benzodiazepine	Respiratory depression in overdose
Beta adrenergic receptor antagonists		Wheezing, shortness of breath
		Acute exacerbation of asthma, COPD (less with beta1 selective drugs)
Anti-craving drugs	Acamprosate	Cough, rhinitis, dyspnea (less severe but frequent)
Stimulant drugs	Methylphenidate	Dyspnea, asthma, pulmonary infiltrate, interstitial pneumonitis, pulmonary vascular disease
Serotonin modulators	Trazodone	Dyspnea, pulmonary infiltrates

TCAs – Tricyclic antidepressants; FGAs – First-generation antipsychotics; SGAs – Second-generation antipsychotics; COPD – Chronic obstructive pulmonary disease

RESPIRATORY DRUGS CAUSING PSYCHIATRIC SIDE-EFFECTS

The respiratory drugs causing psychiatric adverse effects are summarized in Table 13.

Table 13

Drugs used in the respiratory unit causing neurobehavioral symptoms

Classification of drugs	Drugs	Side effects
Antihistaminic	1st generation	Drowsiness and sedation
	2nd generation	No known psychiatric side-effects
Antitussives	Narcotics	Can cause dizziness, drowsiness, sedation
		Patient can get addicted; withdrawal symptoms may precipitate on stopping the drug
	Nonnarcotics	No specific psychiatric side-effects
Bronchodilators	Beta 2 agonist	Tachycardia, tremors; can mimic a panic attack
	Anticholinergics	Occasionally headache
	Xanthine derivatives	Headache, irritability, insomnia
		Seizure and encephalopathy can occur in higher doses
Leukotriene antagonist	Montelukast	Headache, dizziness
	Zafirlukast	Sleep disorder
		Behavioral changes
Steroids	Inhalational	Less side-effect as systemic absorption is less
	Oral	Depression
		Mania
		Psychosis
		Anxiety
		Agitation
		Sleep disturbances
ATDs	Rifampicin	Potent inducer of CYP1A2, CYP2C19, CYP3A4
		Reduce plasma levels of sertraline, nortriptyline, haloperidol, risperidone, clozapine
	Isoniazid	CYP2C19, CYP3A inhibitor
		Documented toxicity with carbamazepine and benzodiazepines
		Can cause acute psychosis
	Pyrazinamide	No clear psychiatric side effects
	Ethambutol	No clear psychiatric side effects
		To be cautiously used in renal impairment patients, and with the psychotropic drugs having renal toxicity

ATDs – Antitubercular drugs

CONCLUSION

The management of psychiatric illnesses in persons suffering from respiratory diseases requires a comprehensive team approach. In liaison psychiatry, many a time the challenges have been thrown with an apprehension by nonpsychiatrists that psychotropics in general are respiratory depressants. In the light of COVID-19 pandemic, this clinical scenario has been dealt with more frequently by mental health professionals as well as specialists from other fields. This guideline has been based on evidence-based medicine supplemented by clinical experiences of the experts which can be used as a ready reckoner, keeping in the mind each case has its own merits and is required to be dealt by situation-based team approach for the benefit of the patient.

Financial support and sponsorship

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Conflicts of interest

There are no conflicts of interest.