| Literature DB >> 35602367 |
Vyjayanthi Nittur Venkataramu1, Harsheel Kaur Ghotra1, Santosh K Chaturvedi2,3.
Abstract
Entities:
Year: 2022 PMID: 35602367 PMCID: PMC9122176 DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_15_22
Source DB: PubMed Journal: Indian J Psychiatry ISSN: 0019-5545 Impact factor: 2.983
General principles of pharmacological management in psycho-oncology
| For all drugs – start low and go slow, i.e., to start from the lowest possible dose and uptitrate gradually based on need and tolerability. To stop at the minimum effective dosage for an individual |
| Look for drug interactions and adverse effect profile of the drug before initiating pharmacotherapy. Due consideration should be given to pharmacokinetic and pharmacodynamic properties of the drug, as people with cancer can have deranged metabolic parameters |
| Not much is known about interaction of chemotherapy, radiation therapy, and newer modalities of cancer treatments on the pharmacological properties of psychotropics. However, the clinician should take a very careful judgment about the medication that might suit the profile of the patient best |
| The utility of nonpharmacological interventions should be emphasized and should begin as a mainstay modality in mild and mild–moderate psychiatric disorders |
| Routine information of use of any ayurvedic, homeopathic, or other medication should be looked at as psychotropics can have interactions with these medications |
Drug interactions of psychotropics and anticancer medications
| Anticancer drug | Psychotropic | Interaction | Mechanism of interaction | Recommendation |
|---|---|---|---|---|
| Carmustine | Naltrexone | Hepatotoxicity | Unknown | Avoid concurrent use. Periodic monitoring of liver function and watching for signs of hepatotoxicity |
| ACDs with* in foot notes | Clozapine | Myelosuppression | Additive synergistic effect | Clozapine should be avoided when person is on treatment with ACDs |
| Cyclophosphamide | Fluvoxamine | Increased dose of ACDs | CYP3A4 inhibition by fluvoxamine | Prescribe with caution, reduce dosage od AD/switch to a safer AD |
| Cyclophosphamide | Bupropion | Increased dose of AD | ACDs inhibit CYP2D6 which reduces clearance of bupropion | Look out for signs of bupropion toxicity like seizures, tremors, anxiety symptoms, agitation, insomnia, or neuropsychiatric symptoms |
| Imatinib | Anti-Alzheimer’s agents** | Increased doses of psychotropics | Imatinib inhibits CYP2D6 and CYP3A4 | Dose adjustments when Imatinib is introduced or taken out from chemotherapy. |
| Imatinib | Bromocriptine, fluoxetine, sertraline | Increased concentrations of both ACDs and AD | ACD and AD Inhibit of cytochrome P450 | To look out for serious adverse effects such as edema, hematologic toxicity, and immunosuppression |
| Methotrexate | Haloperidol | Increased risk of haloperidol-induced photosensitivity | Unknown | Patients were monitored for photosensitivity reactions. Also advised to avoid exposure to sunlight or bright lights |
| Tamoxifen | Antidepressants (Tricyclic AD >SSRI) | Increased risk of drug-induced QT prolongation and torsades de pointes | Additive effects of blocking potassium channels | Measurements of QT intervals and Watch for symptoms of torsades de pointes (syncopal attack, palpitations, and dizziness). In case of QT prolongation, reduce dosage/stop the offending agent |
| Tamoxifen | SSRIs - citalopram, fluoxetine, paroxetine, sertraline | Increased plasma level of tamoxifen | Inhibition of CYP2D6-mediated metabolism of tamoxifen to endoxifen | Dose adjustments of SSRI when tamoxifen is introduced or taken out from chemotherapy |
ACDs with * – Cyclophosphamide; dacarbazine; mechlorethamine; melphalan; procarbazine; temozolomide; rituximab; trastuzumab; bleomycin; doxorubicin; epirubicin; etoposide; irinotecan; topotecan; carboplatin; cisplatin; oxaliplatin; docetaxel paclitaxel; vinblastine; vincristine; vinorelbine; cytarabine; fluorouracil; gemcitabine; methotrexate; pemetrexed; **Anti-Alzheimer’s agents (donepezil; galantamine); **Antipsychotics (aripiprazole; chlorpromazine; fluphenazine; haloperidol; olanzapine; prochlorperazine; quetiapine; risperidone; trifluoperazine; ziprasidone); **Hypnotics and anxiolytics (alprazolam; chlordiazepoxide; clonazepam; diazepam; flurazepam; midazolam; promethazine; propanolol; zolpidem); **Selective serotonin-reuptake inhibitors (citalopram; paroxetine); **Tricyclic antidepressants (amitriptyline; clomipramine; doxepin; imipramine; nortriptyline); **Other antidepressants (mirtazapine; venlafaxine); **Other psychotropics (atomoxetine). ACD – Anticancer drug; AD – Antidepressant; SSRIs – Selective serotonin reuptake inhibitor; QT – Not applicable
Anticancer medication induces psychiatric disorders and their management
| ACD | Psychiatric disorders | Management options |
|---|---|---|
| Asparaginase | Depressive symptoms | Establish a temporal correlation between the starting of ACD and onset of psychiatric symptoms |
| Look for improvement in symptoms during drug-free periods | Delirium | To work in liaison with the primary treating team and inform psychiatric diagnosis and need to adjust/switch/discontinue ACD after weighing out the potential benefits and risks |
| Cisplatin | “Chemobrain” - difficulty in attention, executive functions, short-term memory, recall deficits, and multitasking | |
| Calcineurin inhibitors (ciclosporin, tacrolimus) | Neurotoxicity | |
| Interferons and interleukins | Depression, anxiety, psychosis, suicidal ideation, hypomanic symptoms, and cognitive impairment | |
| Isotretinoin | Depression, suicidal ideation, and psychosis | |
| Antihistamines (1st-generation H1 antagonists >newer antihistamine agents) | Sedation, delirium, cognitive impairment, agitation, and psychosis | |
| Corticosteroids (dose-dependent adverse effects) | Emotional lability, anxiety, irritability, insomnia, cognitive impairments, mood disorders, delirium, reversible dementia, and psychotic disorders |
ACD – Anticancer drug
Anticancer drugs that do not have any known interactions with psychotropics
| Alitretinoin |
| Anastrozole |
| Capecitabine |
| Exemestane |
| Fulvestrant |
| Goserelin |
| Letrozole |
| Leucovorin |
| Leuprolide |
| Lomustine |
| Mesna |
| Mitoxantrone |
Contributors for depression
| Vitamin B12 deficiency |
| Hypothyroidism |
| Folate deficiency |
| Anemia – Iron deficiency |
| Electrolyte imbalance |
Figure 1Stepped care model for delivery of care[6] (adapted with permission)
Description of psychological interventions
| Term | Description |
|---|---|
| Counseling | Generic term used to refer to supportive psychosocial care provided by a qualified professional |
| Psychoeducation | A process of a professional providing information to create awareness, increase knowledge and understanding about a certain condition, in turn, reduce the uncertainty, and improve a person’s mental health |
| Relaxation training | Teaching skills for releasing physical or mental tension using meditative activities, progressive muscle relaxation exercises, or use of guided mental imagery |
| Problem-solving therapy | Focuses on generating, applying, and evaluating solutions to identified problems |
| Cognitive-behavioral therapy | Focuses on identifying, challenging, and changing distorted thoughts and maladaptive beliefs and behaviors, which then reduce negative emotions and lead to positive psychological adjustment |
| Interpersonal therapy | Focuses on problems within interpersonal domains such as grief, role transitions, role dispute or interpersonal deficits. Therapy aims to reduce distress and promote positive psychological adjustment |
| Supportive-expressive therapy | A subjective experience is processed with the help of the therapist in a positive therapeutic relation to enable psychological adjustment (e.g., meaning-centered therapy, dignity therapy, and CALM) |
CALM – Cancer and living meaningfully
Differentiating points for various psychiatric conditions seen in cancer[15]
| Depression | Demoralization | Adjustment disorder | Anxiety disorders | |
|---|---|---|---|---|
| Duration of symptoms (minimum) | 2 weeks | 2 weeks | Usually have a stressful event/change and symptoms start <1 month of change | Symptoms which last for most days of a week for a few weeks |
| Stressor | +/− | + | + | +/− |
| Affective symptoms | Sad/Depressed +/− anxiety | Distress secondary to existential crisis, hopelessness, sense of loss of meaning, and purpose in life | Excessive worry, anxiety, depressive symptoms | Anxious affect |
| Cognitions | Helplessness, hopelessness, worthlessness | Pessimism, helplessness, sense of feeling trapped, looking at self as a failure or as lacking a worthy future, subjective sense of self-incompetence, may extend to hopelessness | Sense of low confidence, difficulty in coping | Fear of negative consequences, usually related to the future |
| Arousal symptoms | Present only when associated with anxiety symptoms | None | Can be present when exposed to stressor | Usually, present |
| Motivation, hedonic pleasure | Amotivation | Motivation present, but dilemma in direction of action | Motivation present, but dilemma in direction of action | Motivation preserved |
| Sleep | Insomnia, usually early morning awakening | Usually sleep intact | Can have insomnia | Can have insomnia |
| Pervasivity | Pervasive | Nonpervasive | Get better with removal of stressor or change in environment | Can be pervasive to situation specific |
Those at higher risk of developing depression
| Inadequate pain control |
| Life stress or loss |
| Past history of depression |
| Level of physical impairment |
| Patients with lung, gastric, oropharyngeal, and gastric cancer |
| Substance use |
| Brain tumor, vascular vulnerability, parkinsonism, Lewy body disease |
| Family history of depression |
| Poor coping skills |
Medications that can cause depression
| Hormonal agents such as aromatase inhibitors, gonadotropin-releasing hormone analogs, and selective estrogen receptor modulators |
| Chemotherapeutic agents - prednisone, dexamethasone, procarbazine, asparaginase, tamoxifen, vincristine, vinblastine, interferon, and interleukin 2 |
| Opioids |
| Amphotericin B |
| Statins |
| Varenicline |
Reversible causes of delirium
| Cancer disease related |
| Brain tumor and/or metastatic illness |
| Paraneoplastic syndrome |
| Ectopic hormone-producing tumor (ACTH, ADH, insulin-like, parathyroid hormone) |
| Cancer treatment |
| Chemotherapy drugs |
| Corticosteroids |
| Radiation therapy – brain |
| Cancer pain drugs |
| Opioids |
| Antidepressants |
| Psychostimulants |
| Infection |
| Other drugs |
| Anticholinergics (Benadryl, tricyclic antidepressants) |
| Anti-Parkinson drugs (levodopa) |
| Centrally acting antihypertensives (methyldopa, reserpine) |
| Corticosteroids |
| H2 blockers (cimetidine) |
| Narcotics (meperidine) |
| Sedative hypnotics (benzodiazepines) |
| Metabolic disturbance |
| Hypoxia |
| Hypercapnia |
| Increased or reduced blood sugar levels |
| Vitamin deficiencies (B12, folate) |
| Electrolyte imbalance (Na, K, Ca) |
| Anemia |
| Dehydration |
| Impaired nutritional status |
| Hepatic or renal dysfunction |
| Environmental |
| Hospitalization |
| Use of physical restraints |
| Catheterization |
H2 – Histamine-2; ACTH – Adrenocorticotrophic hormone; ADH – Anti-diuretic hormone
Risk factors of delirium
| Age of ≥65 years |
| Past history of delirium, dementia, and/or cognitive impairment |
| Preexisting low physical/cognitive activity levels |
| Impaired vision/hearing |
| Dehydration, malnutrition |
| Alcohol abuse/use of psychoactive substances |
| Advanced phase of cancer illness |
| Comorbid medical conditions |
Clinical signs in delirium
| Altered levels of consciousness (alertness or arousal), even amounting to disorientation |
| Disturbances in attention |
| Abrupt onset and rapidly fluctuating clinical course |
| Cognitive disturbances characterized by difficulties in higher mental functioning like apraxia, memory impairment, executive dysfunction, agnosia, visuospatial dysfunction, and language disturbances |
| Psychomotor activity – Increased or decreased |
| Disturbance of sleep cycle, worsening of symptoms with sundowning |
| Mood symptoms - dysphoria, mood lability, euphoria, agitation |
| Perceptual disturbances (hallucinations or illusions) or delusions |
| Disorganization of thought |
| Speech can be incoherent |
| Neurologic findings - asterixis, myoclonus, tremor, frontal release signs, changes in muscle tone |
Subtypes of delirium
| Hyperactive delirium |
| Hypoactive delirium |
| Mixed delirium |
Cognitive interventions in delirium
| Intervention | Method | Explanation | Example |
|---|---|---|---|
| Clarify | Correct misperceptions | It targets the tendency of the patient to misperceive his/her environment. Orientation to place, date, day, time is useful | This room is not a laboratory but an ICU. All people here are trying to help you |
| Verify | Confirm accurate perceptions | Verification and validations compensate for the decreased ability to differentiate between real and not real | “Yes, there is a lot of strange equipment around you, but of all which is necessary to treat you” |
| Explain | Provide information about illness, treatment, and current environment | Explanation compensates for patients’ decreased ability to understand recent events, circumstances, and environment | ‘The reason you are seeing things is because your kidneys are not working well. It is common to have hallucination with such problems” |
| Repeat | Useful information frequently repeated | Patients with delirium have impaired memory. Frequent repetition of all interventions is important | Good evening. You may remember me from this morning. I’m Dr. A, and it is 7 pm, Monday, July 20th |
ICU – Intensive care unit
Emotional interventions in delirium
| Intervention | Method | Explanation | Examples |
|---|---|---|---|
| Acknowledge feelings | Confirm the existence and reasonableness of patient’s feelings | Delirious patients often are in life-threatening situation and receiving intensive medical treatment. They are likely to fear not only death but also pain, abandonment, incapacity, and insanity | I understand that you are feeling frightened. This is a pretty upsetting place. Other patients feel scared at times too |
| Provide familiarity | Well-known people and objects to be provided in their environment | Paucity of familiar sights and sounds intensifies the strangeness and fearfulness of the environment | Same room, same medical team, favorite TV shows |
| Alleviate isolation | Allow for sharing of emotional burden | Emotional burden when shared relieves distress and isolation. | “I can imagine that you fear you might die here” |
| Fostering a sense of control | Allow patients control of the environment, body, treatment whenever possible | For some, complete dependency on caregivers may be anxiety-provoking. Regaining as much control as possible is important | “Here is the remote to adjust your bed, please use it” |
| Balance of hope and realism | Provide realistic information with hope and optimism | For patients who are aware of the seriousness of illness, it is helpful to acknowledge it. To verify their perception of the situation. Denial of this can make them lost trust in their medial team | “Yes, your illness is serious, and operation does come with it risks, but doctors are very confident and hopeful of a positive outcome” |
Enlisting the treatable causes and contributing factors for cancer-related fatigue[40]
| Treatable contributing causes | Comorbid factors |
|---|---|
| Anemia | Infections |
| Sleep-related problems and poor sleep hygiene | Hypothyroidism |
| Poor nutritional status/poor oral intake | Hypogonadism |
| Fluid and electrolyte imbalances | Cardiac/renal/hepatic/pulmonary/neurological dysfunction |
| Emotional distress (anxiety/depression/other) | |
| Low activity levels | |
| Adverse effects of medication/other modalities of treatment | |
| Substance use |
Predisposing, precipitating, and perpetuating factors for insomnia[53]
| Predisposing | Precipitating | Perpetuating |
|---|---|---|
| Female gender | Cancer treatments that cause variations in the level of inflammatory cytokines can alter circadian rhythms/disrupt sleep–wake cycles | Increased daytime sleeping |
| In the elderly, hyper-arousability as a trait | Adverse effects of cancer treatment | Long-term use of prescription/nonprescription drugs |
| Personal or family history | Menopause | Maladaptive cognitions |
| Mood or anxiety disorders | Hospitalization | |
| Distress due to cancer | ||
| Pain, fatigue, or other symptoms | ||
| Corticosteroids/other medications |
Various protocols for breaking bad news
| Spikes - the six-step protocol for delivering bad news[ | Breaks protocol for breaking bad news[ |
|---|---|
| Setting up the interview | Background |
| Perception of patient to be assessed | Rapport |
| Invitation to patient | Explore |
| Knowledge and information sharing to the patient | Announce |
| Patient’s emotions addressed with empathic responses | Kindle |
| Strategy, summary | Summarize |
Guidelines for breaking bad news[1]
| Breaking bad news starts with asking questions and assessing readiness of the patient and family to grasp any information that is being conveyed |
| An appropriate setting and adequate privacy need to be ensured |
| Next, one should find out how much the patient already knows and whether they want any or more information |
| After making sure that the patient is ready, the session should progress in a way that patient and family have a sense of control over the quantity of new information that is being received |
| A “warning shot” or an indication needs to be given at this stage that something serious has happened, after which information is provided in steps |
| After informing the diagnosis, it is important to pause and acknowledge that the news could have shocked or distressed the person |
| Further concerns or queries are explored and discussed, and ventilation is facilitated |
| Session is summarized, and availability for a further session is emphasized |