Clinical practice guideline for management of psychoses in elderly

INTRODUCTION According to Statistics of India in April 2016 population of people above the age of 60 years has increased to 8.6 % of 121 Crores. Age related changes in the Central Nervous System commonly seen in the process of ageing include, Gross brain atrophy, Ventricular enlargement, Selective regional neuronal loss, Remodeling of dendrite, axons and synapses, Appearance of intraneuronal lipofuscin, Selective regional decrease in neurotransmitter and neuropeptides, Selective modification of neurotransmitter metabolism, Possible dysregulation of gaseous neurotransmitter metabolism, Glucocorticoid neurotoxicity, Changes in receptors, Changes in neurotrophins, Changes in signal transduction, Impairment of calcium homeostasis, Possible changes in cell cycle regulations (eg, cyclins), Possible changes in extra cellular matrix proteins (eg. Laminin, proteoglycans), Possible regional decline in cerebral blood flow, Possible regional decline in metabolic rate and Appearance of senile plaque & neurofibrillary tangles. PHARMACOKINETIC CHANGES WITH AGING When we look at pharmacodynamics with aging changes are seen in Neurotransmitter Pharmacodynamics, Dopaminergic system, Dopamine D2 receptor in the striatum, Cholinergic system, Choline acetyl transferase, Cholinergic cell numbers and in Adrenargic system changes are seen in cAMP production in response to beta-agonists, Beta – adrenoceptor number, Beta – receptor affinity and Alpha 2 – adrenoceptor responsiveness. Changes in Gabaminergic system show effect on Psychomotor performance in response to benzodiazepines due to Post – synaptic receptor response to GABA. Psychosis is characterised by loss of contact with reality. DSM -5 defines it by presence of delusions, hallucinations, disorganized thinking (speech), grossly disorganized or abnormal motor behavior including catatonia or negative symptoms. In older populations its etiology, manifestations and treatment deserved special consideration. Psychosis in elderly includes schizophrenia, delusional disorders, psychotic depression, schizo affective disorders, psychotic behavior associated with dementia including Alzheimer disease, parkinsons disease, lewy body and vascular dementias. Commonest among psychoses is schizophrenia which occurs in early age (late second and early third decade of life). In contrast to early onset schizophrenia its presentation after the age of 40 is called late onset schizophrenia and that after the age of 60 is known as very late onset schizophrenia. CHARACTERISTIC FEATURES OF VERY- LATE ONSET SCHIZOPHRENIA Females show significantly higher number than males. Compared with early- or late-onset schizophrenia, very-late-onset schizophrenia is characterized by associated sensory impairment, Social isolation, greater likelihood of visual hallucinations, lesser likelihood of formal thought disorder and affective blunting, lesser likelihood of family history of schizophrenia, greater risk of developing tardive dyskinesia. DRUG-INDUCED PSYCHOSIS Due to process of ageing Elderly patients are suffering from other physical illnesses and often receive multiple medications. Drugs that can produce psychotic symptoms in elderly patients and drug interactions and dosage must be considered when evaluating drugs as causative agents of psychotic symptoms.Table 1: INDIA AGEINGTable 2: Pharmacokinetic Changes with AgingTable 3: Clinical Features and Epidemiology of psychosesTable 4: Characteristics of common causes of psychosis in old ageTable 5: Similarities and differences between early- and late-onset / very late-onset schizophreniaTable 6: Medications used for other physical illnesses which are Associated With Psychotic Symptoms in the ElderlyFACTORS CONTRIBUTING TO INCREASED RISK OF PSYCHOSIS IN ELDERLY Factors which contribute to increased risk of developing psychotic symptoms in old age include age-related deterioration of frontal and temporal cortices, pharmacokinetic and pharmacodynamic changes, Neurochemical changes, Social isolation, Sensory deficits, Cognitive decline and Polypharmacy. ASSESSMENT AND EVALUATION Systematic observation of the patient with concentration on the following areas: Assess symptoms to identify the problem. Assess antecedents and consequences Clarify negative effect of the symptoms on the patient and caregivers because psychotic symptoms that do not have a negative impact may not require treatment. Ascertain possible causes for the symptoms e.g. environmental causes. Whether the patient has a negative view of the caregiver or inability to understand the intentions of caregivers. Whether the patient suffers from social isolation or sensory deprivation. Whether the patient misinterprets the environment and situations. Diagnostic criteria for schizophrenia (adapted from DSM-IV-TR) Characteristic symptoms 2 (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated): delusions hallucinations disorganised speech, eg frequent derailment or incoherence grossly disorganised or catatonic behaviour negative symptoms, ie affective flattening, alogia, or avolition SOCIAL/OCCUPATIONAL DYSFUNCTION Duration: continuous signs of the disturbance persist for at least 6 months Exclusion of schizoaffective and mood disorder Exclusion of substance/general medical condition Agitation: The term agitation refers to a range of behavioral disturbances including aggression, combativeness, shouting, hyperactivity and disinhibition. The most common cause of agitation in old age is delirium followed by dementia. Other conditions like Schizophenia, BPAD, Psychotic Depression may also cause agitation in this age group. Preventive Interventions Reorientation should be ensured by familier person and optimal level of sensory input. Loud noise should be avoided and patient should be allowed to have adequate and uninterrupted sleep. Hydration should be maintained either orally or intra venously. Physical restrainment should be discouraged as it may further escalate the agitation. The use of unnecessary medications should be avoided. The management strategy should follow the basic principles as outlined before Pharmacological Interventions If agitation is severe enough to render patient himself or others in danger, rapid sedation is necessary. Pharmacologic options include the benzodiazepines and the typical and atypical antipsychotics agents. Intravenous, intramuscular or oral route may be preferred considering the level of agitation and associated physical condition of the patient Summary of the Initial Evaluation and Management of the Agitated Elderly Patient Provide immediate interventions for urgent medical conditions Assume the etiology of the agitation is delirium Assess for underlying etiology or exacerbating factors and manage appropriately Review history of present illness, medical history and medication profile Provide optimal environmental and supportive interventions Pharmacological agents should be considered when the patient has the potential to harm themselves or others, or is impeding medical evaluation and management Dose must be adjusted considering age of the patient DELUSIONAL DISORDER Prevalence of Delusional disorder have been reported 0.03% of elderly population. Delusional disorder may account for 1- 4 % in admitted elderly population. Delusional parasitosis tend to occur more frequently specially in females. To establish the diagnoses of delusional disorder, clinician must rule out the possibility delirium, dementia, psychotic disorders due to general medical conditions or substance use, schizophrenia, mood disorders with psychotic features, significant organic brain syndrome or physical illnesses like pellagra. These patients may be treated with risperidone, olanzapine, quetiapine. Treatment should be started at low dose and gradually be titrated upward. CHARACTERISTIC SYMPTOMS OF DELUSIONAL DISORDER Non bizarre delusions, ie involving situations that occur in real life, such as being followed, poisoned, infected, loved at a distance, or deceived by spouse or lover, or giving a disease) of at least 1 month's duration, Not meeting the criteria for schizophrenia, No marked social or occupational dysfunction, Exclusion of mood disorder, Exclusion of substance abuse. Subtypes: Erotomanic type: delusions that another person, usually of higher status, is in love with the individual. Grandiose type: delusions of inflated worth, power, knowledge, identity, or special relationship to a deity or famous person. Infidelity type: delusions that the individual's sexual partner is unfaithful Persecutory type: delusions that the person (or someone to whom the person is close) is being malevolently treated in some way Somatic type: delusions that the person has some physical defect or general medical condition Mixed type: delusions characteristic of more than 1 of the above types but no 1 theme predominates BIPOLAR AFFECTIVE DISORDER In elderly very late onset, BPAD is estimated between 0.25 to1 %. Studies are limited and conflicting. Increased depressive episodes with psychotic features in one study and no difference in another. High prevalence of thought disorders in elderly and high rate of aggression and irritability in early onset and younger adults. Drug treatment advised is atypical antipsychotics except clozapine. Olanzapine-Fluoxetine combination has strong evidence in mixed bipolar patients. PSYCHOTIC DEPRESSION Late onset depression(>60 Yr) is more commonly associated with delusion than the early onset. Delusion of persecution is more common in this age group. Nilhistic delusion may also occur more commonly but hallucinations are less common. Pharmacological treatment includes use of SSRI (Citalopram, escitalopram, fluoxetine, paroxetine, and Sertraline). Tricyclic antidepressant can be tried in those patients who have not responded to SSRI and can tolerate the side effects. In severe cases ECT continues to be the most effective treatment. Diagnosis of Late-Life Psychoses Late life Psychoses caused by a psychiatric disorder is called primary and that due to a medical or neurological disorder is considered secondary. About three fifths of psychotic disorders in later life are due to a secondary condition. Delirium, Drugs, alcohol, toxins, Depression and other affective disorders are most commonly associated with late life psychoses, Dementia, Delusional disorder and schizophrenia spectrum disorder are main stay of the diagnostic categories. Clinical presentations commonly seen which raised suspicion of secondary causes of psychosis are as follows:- Late age of onset of the presenting psychiatric symptoms Family history and past history of mental illness less commonly observed. Severity of symptoms more than expected Abrupt personality change followed by psychopathology Comorbid medical conditions. Abnormalities of cognition like memory and consciousness Low response to psychiatric treatment PLANNING INTERVENTION The following points should be kept in mind: Needs of the particular patient and the cause of the symptoms. Where is the intervention required? Patient or at the environment or members of staff or the general system of care. Regular assessment and re-evaluation of the intervention is required to monitor improvement FORMULATING A TREATMENT PLAN Points to remember before prescribing medication in elderly Magnitude of effect (clinical response) = Pharmacodynamics (potency of a drug for binding to the receptor) x Pharmacokinetics (drug concentration at the site of action x biological variance (individual biology of he patient and targeted disease process. In elderly medical complication of pharmacotherapy alone constitute a highly significant treatable health problem. Adverse reaction to drugs of all types is seven times higher in those aged 70 to 79 years, than in those 20 to 29 years old. Non compliance with therapy is a major problem for psychiatric patients, and this dilemma is exacerbated with age. Age related health problems combines with physiological changes to increase the probability of adverse effect from medication which in turn increase the likelihood of non compliance. Complexities of medication regimens are further complicated by communication difficulties arising from impaired hearing, cognitive impairment, language & cultural difficulties. MANAGEMENT Pharmacological Psychosocial interventions Step 1. Rule out organic and environmental causes of psychotic symptoms e.g. deafness, poor vision, chronic pain, dehydration, deranged metabolic functions and constipation, medications that can cause/aggravate psychotic. Step 2. Decide whether the symptoms are causing distress or disruption in the patient's life to warrant treatment with antipsychotic medication, carefully evaluate potential risks due to side-effects and benefits of symptom relief with the use of antipsychotics. A common example is of an older lady with chronic schizophrenia presenting with musical hallucinations that are not distressing. A simple social intervention such as organising day care to reduce her loneliness or provision of a hearing aid may solve the problem as compared to starting/increasing the dose of antipsychotics. TREATMENT OF LATE ONSET SCHIZOPHRENIA Conventional antipsychotics Significant improvement in psychotic symptoms with the use of haloperidol and trifluoperazine (10-30mg a day) were reported in the 1960's. Depot antipsychotics can be useful in older patients with compliance problems. Use of low doses of depot antipsychotics such as flupentixol decanoate or fluphenazine decanoate every two weeks can produce a better clinical outcome. One of the common dilemmas encountered in clinical practice is the management of an older patient with chronic schizophrenia who has been stable on a depot for a number of years but has now started to develop extra pyramidal symptoms. There is usually an associated element of cognitive and functional decline. The first step is to review the dose of depot medication as older people do not need higher doses and can easily be managed on a smaller dose as discussed above. The second step would be to either consider using a small dose of anticholinergic medication such as procyclidine or consider using an atypical antipsychotic in oral or depot form – only risperidone depot (Risperdal Consta) is available. The clinical decision-making process would involve weighing these options against the risk of relapse, severity of illness and the overall quality of life of the individual patient. Atypical antipsychotics The first choice treatment for older patients now considered to be safe and effective are atypical antipsychotics due to their better side-effect profile in comparison with conventional antipsychotics. Risperidone The most extensively studied atypical antipsychotic in the older population is risperidone. It is effective as a first-line antipsychotic agent, is well tolerated in lower doses (1.5-6mg daily) and produces significant clinical improvement in older patients with schizophrenia. Olanzapine Olanzapine is claimed to significantly improve symptoms of schizophrenia and extra pyramidal side effects. However the data available on the use of olanzapine in older patients population of schizophrenia are limited.Table: No title available.Quetiapine Quetiapine has been reported to be safe in older people though the data available are limited. It has been reported to be safely used in doses up to 750mg daily in divided doses with a warning that in order to avoid potential side-effects like postural hypotension and dizziness, it was better to start at a lower dose and titrate slowly upwards. Aripiprazole Aripiprazole is less likely to cause extra pyramidal symptoms, sedation, weight gain and cardiovascular side-effects. However, there is a paucity of data on its use, safety and dosing strategies in older people. It has been reported to improve both positive and negative symptoms and caused fewer side-effects. Dosing regimens should be tailored according to the needs of individual patients. It is the latest of the atypical antipsychotics with a unique mode of action of being a partial agonist at D2 receptors. Clozapine The usefulness of clozapine in treatment-resistant early cases is well established, but concerns about toxicity and the need for monitoring white cell counts has led to a limited use in older patients. In a review of clozapine use in older psychiatric patients, the authors concluded that most patients showed moderate to marked improvement of psychotic features at a relatively low mean dose of 134mg per day, and cautioned that agranulocytosis may occur more frequently in older patients. In view the above-mentioned risks, clozapine is not a first-choice antipsychotic for older patients and should only be used in cases of treatment resistance and severe TD. NON- PHARMACOLOGICAL MANAGEMENT Electroconvulsive therapy It appears that with the introduction of a variety of typical and atypical antipsychotics, the use of ECT in older patients with schizophrenia has declined in clinical practice. A better response to ECT in patients of late paraphrenia presenting with dominant affective symptoms has been reported. Psycho-education Depending upon the diagnosis of the patient psycho-education has to be provided to the patient and the care givers regarding disease, its causes, likely course of illness, treatment options and selection of treatment with its rationale and an emphasis on regularity of treatment, follow up care. Cognitive behavioural therapy Cognitive behavioural techniques aiming at modification of delusional beliefs and control over hallucinations has been widely reported. Unfortunately there have been few research studies conducted on the use of these techniques in older patients. The possibility of their use in helping older patients gain insight into their illness and address coping strategies to help them live a meaningful life. In 2000 a novel approach of an integrated cognitive behavioural and social skills training intervention for older people with schizophrenia was developed. This treatment approach suits the needs of older patients and aims to reduce their cognitive vulnerabilities, improving abilities to cope with stress and adherence to other forms of treatment. Psychosocial therapies Psychosocial interventions aimed at improving independent living and social skills is well established. Such interventions may be of importance in older patients as a significant number fail to show a complete response to antipsychotics. A combination of interpersonal and independent skills training, along with the standard occupational therapy, has been found to be associated with improved social functioning and independent living. Choice of treatment settings Treatment setting includes management in indoor setting followed by treatment in the OPD. Since the psychotic illness in elderly needs adequate evaluation, assessment and management, indoor treatment should be preferred. General ward with other psychotic patients is not advisable. Patients should be given individualized care preferably in a single room with least sensory stimulation and intensive nursing care. It is advisable to keep close care givers with the patient with an advise to keep the patient oriented to time, day, date and place. In case of medical comorbidity physician on call should be readily available. Management of maintenance phase Appropriate reduction in the doses of the drugs given during acute phase and considering the improvement in the patients clinical status should be made and first onset late psychoses should be treated for at least one year. Treatment may be continued longer in case of relapse of the illness. When to stop treatment As a rule, medication should be started at the low dose with gradual upward titration until the clinical response is observed. Once the optimal response is achieved, the same effective dose should be continued for another 2 to 4 months with subsequent gradual tapering and maintenance treatment as advised. Optimal duration of treatment with antipsychotic medications largely depends upon residual clinical picture and psychosocial context of the patients and clinical judgment of treating psychiatrist. Special issues Medical comorbidities Secondary conditions are responsible for about three fifth of psychotic disorders in elderly. Hence, a very careful and comprehensive examination including history, physical and neurological evaluation remains crucial for accurate diagnoses and treatment. Treatment in such cases should be based on underlying medical condition. First line of treatment must focus on behavioral and environmental strategies, however use of antipsychotics is indicated in case of symptom severity. Treatment should be tailored according to patients need and should be time limited and dose limited. It is advisable to avoid clozapine, olanzapine and conventional antipsychotics in patients with major metabolic conditions like diabetes, dyslipidemia, obesity etc. similarly in cardiac patients clozapine, ziprasidone and conventional antipsychotic should be avoided. It is preferable to use risperidone and quetiapine in such cases. Common Comorbid medical causes of psychosis in elderly persons have been mentioned below which should be taken in to consideration while evaluating and treating psychoses in older adults.Table: No title available.Metabolic conditions associated with psychoses include Vitamin B12 deficiency, Folate deficiency, Electrolyte abnormalities, Sodium, Potassium, Calcium, Magnesium, Acute intermittent porphyria, Hepatic encephalopathy, Uremic encephalopathy, Other nutritional deficiencies, Anoxia/hypoxia, Hypercarbia, Infections, Meningitides, Encephalitides (e.g., herpes, etc.), Neurosyphilis, HIV/AIDS, Pneumonia, Neurological, Parkinson's disease, Epilepsy, Temporal lobe epilepsy, Grand mal, Non-convulsive status epilepticus, Subdural hematoma, Cerebrovascular events, Huntington's disease, Multiple sclerosis, Amyotrophic lateral sclerosis, Tumors, Temporal lobe—auditory hallucinations, Occipital lobe—visual hallucinations, Limbic—delusions, Hypothalamus—delusions, Limbic encephalitides, Autoimmunereference, Paraneoplastic syndromes, Systemic lupus erythematosis, Vasculitides, Sleep disorders (narcolepsy), Other genetic/heritable conditions, Likely to have been diagnosed in childhood, Endocrine, Hypo-/hyperthyroidism, Adrenal disease, Hypo-/hypoglycemia and Hypo-/hyperparathyroidism Psychiatric comorbidities Common psychiatric comorbidities observed with psychoses in elderly include depression, dementia, delirium, delusional disorder, anxiety/agitation, which needs to be addressed after ruling out possible secondary causes if any (medical disorders/electrolyte/metabolic disturbances, drugs). Management of co morbidity has to be planned primarily by non pharmacological management and medication if unavoidable. Substance dependence Multiple substances have been implicated in causation of psychoses in elderly population either during intoxication or withdrawal. First line of treatment in such cases should focus on withdrawal of offending substance, appropriate treatment of non psychotic withdrawal symptoms and management of psychotic symptoms with appropriate antipsychotic in half the adult dose. Psychosocial interventions like CBT, Motivational enhancement therapy should be encouraged at the clearance of cognitive symptoms if any. Risk of Suicide Person aged 75 years or above have higher suicide rates among all age group. Suicide attempts in elderly population are often long planned and involves more lethal methods as compared to younger counterparts who often have communicative act and impulsive attempts. Major depression is the most common cause in this population who attempt or complete the suicide. Primary psychotic disorders including schizophrenia, schizoaffective illness, and delusion disorder, as well as anxiety disorders, tend to be present in lower proportions. Physical illness also plays a significant role in suicidal behavior in this population. Key Risk factors Recent Stressful life events Presence of chronic/terminal illness with diaability Recent bereavement or relationship breakdown Widow/widower Evidence of depression /loss of interest or losas of pleasure Evidence of withdrawal Warning of suicidal intent Evidence of a plan to commit suicide History of psychosis Evidence of persecutory voices/beliefs Family history of serious psychiatric problems or suicide Presence/influence of hopelessness Prior suicide attempt History of socioeconomic deprivation/financial worries History of alcohol and/or drug misuse Management of side effects of medication Drug side-effects Movement disorders like tardive dyskinesia (TD), can be more persistent and disabling in older people. TD can lead to a number of physical and psychological complications such as difficulty in eating and swallowing, weight loss, falls, poor balance and depression. The risk of developing TD from conventional antipsychotics is five to six times higher in older people and recent studies indicate that atypical antipsychotics may have a lower risk of TD and may therefore be safer in this age group. A large multicentered study comparing the mortality risk posed by typical and atypical antipsychotics reported a 37 per cent higher risk of death in people who went on a typical antipsychotic and that risk was dose dependent. In a clinical setting, it is useful to follow the principle 'start low and go slow’ for prescribing antipsychotics to older people. CONCLUSION Psychotic symptoms in older people can be caused by a wide range of factors including common physical problems, environmental factors, cognitive decline and functional illnesses are responsible for psychotic symptoms in older people. The diagnosis and management of psychosis in older people is a complex process that should take into account all these factors and should not be limited to the use of antipsychotic medication alone.