Shrivastava S

Psychotic disorders are a serious condition where a person experiences a short period of losing contact with reality. It involves the number of psychotic illness. Risks associated with psychotic disorders are significant but with prompt care and treatment they can be prevented.

Treatment of psychotic disorders involves the availability of number of medication, psychosocial treatment, complementary therapies and the pace of treatment. There is no medical test which can diagnose psychotic disorders, for this reason it is very important for health professional to get a full picture of the various patients suffering from psychotic disorders. This review covers the number of psychotic disorders with their brief explanation and treatment, which can be fruitful for health professional to treat psychiatric patients.

Introduction

Psychotic disorders are a group of serious illnesses that affect the mind. These illnesses alter a person’s ability to think clearly, make good judgments, respond emotionally, communicate effectively understand reality and behave appropriately. When symptoms are severe, people with psychotic disorders have difficulty staying in touch with reality and often are unable to meet the ordinary demands of daily life. The major symptoms of psychotic disorders are hallucinations and delusions. Hallucinations are unusual sensory experiences or perceptions of things that are not actually present. Delusions are false beliefs that are persistent and organized. The exact cause of psychotic disorders is not known, but researches believe that many factors may play a role like inheritance, environmental factors (including stress and drug abuse) and imbalance of certain chemicals (dopamine) in the brain.

About 1% of population world wide suffers from psychotic disorders. These disorders most often first appear when a person is in his/her late teens, 20s/30s. There are no laboratory tests to specifically diagnose psychotic disorders. Most psychotic disorders are treated with a combination of medications and psychotherapies ¹ . There are different types of psychotic disorders covered by this review, with their overview of treatment that is discussed below;

1. Patients with bipolar disorders

Bipolar disorder, also known as manic depressive illness, is a brain disorder that causes unusual shifts in a person’s mood, energy, and ability to function. More than 2 million American adults ² or about 1 percent of the population age 18 and older in any given year ³ has bipolar disorder. Bipolar disorder typically develops in late adolescence or early adulthood. However, some people have their first symptoms during childhood, and some develop them late in life. Bipolar disorder causes dramatic mood swings from overly high and/or irritable to sad and hopeless and then back again, often with periods of normal mood in between. Severe changes in energy and behavior go along with these changes in mood. The periods of highs and lows are called episodes of mania and depression.

The patient with unipolar depression either respond to antidepressants (partially or completely) or does not, but in bipolar illness antidepressant may a) fail to budge a depressive episode b) lead to partial response with residual depression c) lead to temporary euthymia followed by later relapse depression d) cause a transient hypomania followed by euthymia e) produce a transient hypomania followed by a full-blown acute mania f) lead directly to a full acute manic episode or g) lead to persistent euthymia. The most common response for noncompliance is side effects, with weight gain (lithium and valporate) and memory impairment being the most frequent complaint ⁴ . 

Overview of treatment

Mood stabilizers (lithium with valproate, gabapentin), neuroleptics agents (haloperidol), antidepressant and benzodiazpines can be used for treatment of euthymia. The recommended treatment algorithms for bipolar disorder have been shown in fig. 1.

2. Patients with schizophrenia

Schizophrenia which affects approximately 1% of the population, usually begins before age 25, persist throughout life and affects people of all social classes. Both patients and their families often suffer from poor care and social ostracism because of widespread ignorance about the disorder. Clinicians should appreciate that the diagnosis of Schizophrenia is base entirely on the psychiatric history and mental status examination ⁵ .

The patients with schizophrenia are inherently difficult to treat because schizophrenia is a chronic, debilitating and often incapacitating mental illness. However schizophrenia falls along a continuum of severity and that numerous intrinsic and extrinsic factors makes some patients much more difficult to manage than others. The time prevalence of schizophrenia is approximately 1% ⁶ . Both positive and negative symptoms may initially respond to classical neuroleptics ⁷ , most studies showed strongly preferential long-term effect on positive symptoms. Despite the evident benefit of neuroleptics, about 40% of treated patients show moderate to severe psychotic symptoms and about 8% shows no improvement or become worse ⁸ . 

Overview of treatment

i) Pharmacological options and Electro convulsive therapy (ECT)

a) Depot neuroleptics (fluphenazine) b) Atypical agents (clozapine, ziprasidone and quetiapine) c) Augmentation strategies: Antidepressant (fluvoxamine, fluoxetine, and citalopram), Mood stabilizers (lithium and carbamazepine) and Combining antipsychotic (clozapine or risperidone plus conventional neuroleptics. ECT is particularly applicable in patients with first-break episodes, especially those marked by excitement, over activity, delusion or delirium, to avoid the debilitating effects of chronic illness ⁹ .

ii) Miscellaneous agents

 Some other miscellaneous agents used for treating Schizophrenia are given in table 1 and 2.

3. Patients with depression

About 9.5 % of the population suffers from a depressive illness ¹⁰ . Depressive illnesses often interfere with normal functioning and cause pain and suffering not only to those who have a disorder, but also to those who care about them. Serious depression can destroy family life as well as the life of the ill person. Most people with a depressive illness do not seek treatment, there are now medications and psychosocial therapies such as cognitive/behavioral, “talk,” or interpersonal those ease the pain of depression. A depressive disorder is an illness that involves the body, mood and thoughts. It affects the way a person eats and sleeps, the way one feels about oneself and the way one thinks about things. Three most common depressive disorders are Major depression, Dysthymia ( severe depression) and Bipolar disorder (manic-depressive illness).

Depressions are common challenge in clinical practice and have high morbidity and mortality. The initial antidepressant treatment focuses on using full doses for at least 6-8 weeks ⁸ . Poor response can also be due to poor absorption, noncompliance or physiological issues such as patients not wanting to accept that they need medication ^11,12 . Psychotic depression, which occurs in up to 15% of severely ill patients, is often misdiagnosed. Bipolar depression is usually more difficult to treat than unipolar depression. Atypical depression is characterized by mood reactivity, increase in both sleep and appetite, sensitivity to rejection and leading paralysis ¹³ . Dysthymic disorders often present with only mild or moderate symptoms ¹⁴ .

Overview of treatment

Pharmacotherapy and psychotherapy

Pharmacological option for the treatment of resistant depression focus on optimization of antidepressant monotherapy, switching to another antidepressant, augmentation, or a combination of two or more antidepressants. Medication and alternative augmentation strategies associated with depression are shown in table 3 and 4. The best outcomes are seen when psychotherapy and medications are combined ¹⁵ .

4. Patients with anxiety disorders

Anxiety disorders are of four types, these are:

A) Social phobia-

This involves excessive anxiety in wide variety of social situation. Social phobia, with 13.3% lifetime prevalence, is the third most common psychiatric disorder in United State . The onset is typically between 13 and 20 year of age, onset is rare after 25 years ¹⁶ of age.

Overview of treatment-

Pharmacotherapy and Psychotherapy

SSRIs (fluvoxamine, sertraline), MAOIs (phenenzine), Benzodiazepines (alprazolam, phenenzine) and ß- blockers (propanalol) have been used. The patients can be treated with individual or group therapy; CBT group is especially helpful, as it provide an opportunity for exposure practice in the presence of therapist.

B) Obsessive-compulsive disorder (OCD) -

It is a chronic illness that has waxing and warning course, has a high combordity with other anxiety and mood disorders, and can be disabling.

Overview of treatment

Pharmacotherapy and Psychotherapy 

The SRIs, which include the SSRIs and clomipramine, are the first line choice for OCD treatment. The other TCAs and MAOIs have shown little efficacy in OCD. ERP, have widely used in OCD, controlled studies of ERP have reported improvement of as much as 60% to 85% ^17,18 .

C) Generalized anxiety disorder-

The lifetime prevalence for generalized anxiety disorder is 5.1%. Generalized anxiety disorder is defined as excessive anxiety and worry about number of events of activities, accompanied by physiological symptoms.

Overview of treatment

Pharmacotherapy and Psychotherapy

Benzodiazepine, antidepressant and buspirone have all been purported to be effective drug treatment for generalized anxiety disorder. Number of studies concluded that cognitive therapy was most effective. It has also been helped by supportive, nondirective therapies and anxiety-management training ^19,20 .

D) Panic disorder-

The essential feature in panic disorder is the unexpected panic attack, which is a discrete period of intense fear and discomfort with symptoms such as dizziness, increased heart rate, sweating, shortness of breath and paresthesias, as well as fear of dying, loosing control or going crazy.

Overview of treatment

Pharmacotherapy and Psychotherapy

Benzodiazepine (clonazepam and lorazepam), SSRIs (fluvoxamine and paroxetine), TCAs (imipramine and clomipramine) and MAOIs has been used in the treatment of panic disorder. The overall response rate for those completing CBT treatment was 89% and is equal in efficacy to antidepressant medication ^21,22 .

5. Patients with posttraumatic stress disorder (PTSD)

According to DSM-IV ²³ , PTSD may develop in those who experienced or witness with “horror, terror or helplessness” a traumatic event involves real or perceived threat to life or physical integrity. PTSD is specified as chronic when the symptoms persist for 3 months or more. The lifetime prevalence of PTSD has been estimated at 24% among trauma survivors and at 9% in the general population ²⁴ .

Overview of treatment

Pharmacotherapy and Psychotherapy

SSRIs (fluoxetine, sertaline and paroxetine), TCAs (amitriptyline and phelelzine) and mood stabilizers (lithium, carbamazepine and valpronic acid) can be used. The cognitive-behavioral intervention for PTSD generally employ, either alone or in combination. In this combine therapy shows more efficacy than individual therapy.

6. Patients with borderline personality disorder (BPD)

There are three distinct types of borderline patients. Type I patients have mild cases of BPD, borderline trait disorder in these patients manifest the same dysphoria, cognitive disturbances and same interpersonal difficulties as type-II patients, Type II borderline patients are intermittently self-destructive, particularly when they are fear of being abandoned by someone on whom they depend. Type III borderline patients lead very chaotic lives, with areas of self-defeating behaviors ²⁵ .

Overview of treatment

Sometimes BPD patients are so depressed, out of control and/or psychotic in their thinking that they need to be hospitalized. The medication includes: antipsychotics, antidepressants, anticonvulsants or mood stabilizers, anxiolytics and lastly naltrexone.

7. Patients with dissociative disorder (DID)

Patients with dissociative disorder suffer transient or chronic “disruption in the usually integrative function of consciousness, memory, identity or perception of the environment”. Various dissociative disorders involve: dissociative amnesia, dissociative fugue, dissociative identity disorders, depersonalization disorders, dissociative disorders not otherwise specified (NOS) and dissociative trace disorders.

Overview of treatment

The treatment of DID follow the paradigm of the treatment of trauma ²⁶ . The stages of therapy have been categorized as; a) establishing the psychotherapy b) preliminary intervention c) history gathering and mapping d) metabolism of the trauma e) moving towards integration/resolution f) integration/resolution g) learning new coping skills h) solidification of gains/working through i) follow-up ²⁷ .

8. Patients with eating disorder

Eating disorder of various kinds has been reported in upto 4% of adolescent and young adult student. It shows a wide range of symptoms as well as variation in severity in different individuals. It is of two types; Anorexia nervosa and Bulimia nervosa.

a) Anorexia nervosa-

It is characterized by as a disorder in which people refuse to maintain a minimally normal weight, intensely fear gaining weight and significantly misinterpret their body and its shape. DSM-IV identifies two subtype of Anorexia nervosa- the restricting type and the binge-eating or purging type ⁵ .

Overview of treatment

Pharmacotherapy and psychotherapy

Cyproheptadine, clomipramine and amitriptyline have been used for treatment of anorexia nervosa. A Congitive and behaiour therapy principle has also been found to be effective. Dynamic expressive supportive psychotherapy is sometimes found to be very beneficial in the treatment of anorexia nervosa. One controlled trial study on 80 patients shows that family therapy is more effective ²⁸ as compare to dynamic expressive supportive psychotherapy.

b) Bulimia nervosa-

Bulimia is merely a term that means binge eating, which is defined as eating more food than most people in similar circumstances and in a similar period of time, accompanied by a strong sense of losing control ⁵ . Estimates of bulimia nervosa range from 1-3% of young women. Bulimia nervosa is often present in normal young women, but sometimes patients have a history of obesity. Approximately 90% of people who have eating disorders are female ²⁹ .

Overview of treatment

 Pharmacotherapy and psychotherapy

Antidepressant medication such as SSRIs (fluoxentine), imipramine, trazodone and MAOIs have been helpful in bulimia nervosa. Studies showed that combination of cognitive behavioral therapy and psychodynamic treatment of patients and medications is the most effective treatment for bulimia nervosa.

9. Patients with substance abuse

DSM-IV refers to brain-altering substances as substance (alcohol, amphetamine, caffeine. cannabis, cocaine, nicotine, opoid, inhalent etc.) and to the related disorder as substance related disorder. Some substance can affect both internally perceived mental state, such as mood and externally observable activities such as behaviour. Substances can cause neuropsychiatric symptoms indistinguishable from those of common psychiatric disorder with no known cause. According to classic theories, substance abuse is a masturbatory equivalent, a defense against anxious impulses or a manifestation of oral regression. These patients with comorbid disorder are commonly referred to as dual-diagnosis patients. The DSM-IV reveals a long lists of substance related disorders, including intoxication and withdrawal syndromes for both alcohol and other drugs ⁵ .

Overview of treatment

Pharmacotherapy and Psychotherapy

It includes serial, parallel and integrated treatment model ³⁰ . Very few researches have been carried out in the pharmacological treatment of patients with dual disorders due to patient ambivalence. It has been divided into several categories: a) antagonist or partial antagonists b) anticraving agents c) anti-drug-seeking agent d) aversive agents e) agent for comorbid psychiatric problems.

10. Patients with dementia or traumatic brain injury (TBI)

Dementia, particularly Alzheimer’s disease, is a common cause of behavioral disturbances in the elderly and psychotic Disorder due to Traumatic Brain Injury (PDTBI) is the current DSM-IV diagnosis given to individuals who develop a psychosis after a traumatic brain injury (TBI) ³¹ .

a) Dementia (Alzheimer’s) disease-

Dementia is a dimution in cognition in the setting of a stable level of consciousness. It is characterized by multiple cognitive defects that include impairment in memory, without impairment in consciousness. It is a common cause of behavioral disturbances in the elderly ⁵ . It is a progressive neurodegenerative syndrome with neuropsychological and neuropsychiatric manifestation. The cognitive functions that can be affected in dementia include general intelligence, learning and memory, language, problem solving, orientation perception, attention and concentration, judgement and social abilities ³² .

Overview of treatment

The only psychotropic agents currently available and unique to the management of alzheimer’s are cholinergic agents. Other drugs like physostigmine, metrifonate, rivastigmine (6-12mg) and galantamine (16-24mg) also have been used to reduce behavioral abnormalities in Alzheimer’s disease.

b) Traumatic brain injury-

Neuropsychiatric disorders are common complication of TBI, ranging from mild personality changes to delirium, dementia, psychosis and severe personality alteration.

Overview of treatment

These problems are managed by means of behavioral, environmental, psychosocial and pharmacological strategies. Drugs like dopamine agonist (amantadine), neuroleptics (haloperidol), newer antipsychotics (risperidone, clozapine and quetiapine), benzodiazepines and anticholinergic antidepressants have also been used.

11. Patients with comorbid medical illness

Comorbid medical illness present major diagnostic and treatment challenges in the treatment of refractory psychiatric illness. For this accurate diagnosis and effective treatment will be enhanced by familiarity with specific comorbid medical conditions and their relationship to psychiatric illness ³³ .

a) Psychiatric patients with comorbid cardiovascular disease:

Research suggests that depression is associated with the development of ischaemic heart disease and that for those with pre-existing cardiovascular disease ³⁴ .

Overview of treatment

Tricyclic antidepressants (TCAs may be more efficacious than SSRIs), Non-Tricyclic antidepressants (buproprion, mean daily dose 442 mg, venelafaxin > 200mg, mirtazapine and nefazodone), Mood stabilizers (lithium therapy, carbamazepine, oxcarbazepine and topiramate).

b) Psychiatric patients with comorbid Diabetes Mellitus:

It has been suggested that major depression increases the risk of non-insulin-dependent diabetes mellitus (NIDDM) ³⁵ . The prevalence of major depression in diabetes considering both type-I and type-II is about 15-20% ³⁶ .

Overview of treatment

Tricyclic antidepressants, Non-Tricyclic antidepressants {(hydrazine MAOIs (i.e. phenenzine) and nonhydrazine MAOIs (i.e. tranylcypromine)}, ECT has been used.

c) Psychiatric patients with comorbid respiratory disease:

An increased prevalence (8-37%) of panic and mood disorder is associated with chronic obstructive pulmonary disease (COPD). The COPD patient demonstrates the complex interactions of comorbid respiratory and psychiatric symptoms, especially dyspnea and anxiety ³⁷ .

Overview of treatment

Tricyclic antidepressants (doxepin 105 mg/day), Non-Tricyclic antidepressants ³⁸ (In one study six COPD patients, only 3 with anxiety/mood diagnoses, all reported improved sense of well being and 5 out of 6 improved on activities of daily living after 6 weeks of sertraline 100mg/day) and Mood stabilizers (Smaller lithium doses).

Conclusion:

Psychiatric patients need a more careful and complete diagnosis that could lead to complete and better treatment. In the psychiatric disorder, it appears that resistance to treatment has become increasingly common. To treat psychiatric patients two highly specific approaches, personal therapy and family psychoeducation, is more effective than medication alone. The conditions, which do not respond to medication and require long-term psychotherapy, the treating clinicians must be alert to the state of the therapy, monitoring its progress as a process, and be sensitive to the potential responses. Poor medication compliance is probably the most important factor in treatment non-response. The successful treatment of psychiatric disorders rest on two key elements: the critical role of the psychiatrist in coordinating somatic and psychosocial treatments and the avoidance of either well-intentioned under-treatment or haphazard treatment.

Studies clearly revealed that there is need of proper assessment of the efficacy of medication, cognitive-behavioral therapy and their combinations. Greater attention to be paid to the individual’s characteristic of patients suffers from psychiatric disorder. Health professional involved in treating, need to have an optimistic nature, a good sense of humor and iron constitution. Common sense is probably a more important tool for health professional to possess than a wish to conduct a sophisticated psychodynamic psychotherapy.

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Abbreviations

DID- Dissociative identity disorder

PTSD- Post traumatic stress disorder

OCD- Obsessive compulsive disorder

ECT- Electroconvulsive therapy

SSRIs- Selective serotonin reuptake inhibitors

TCAs- Tricyclic antidepressants

MAOIs- Monoamine oxidase inhibitors

AD- Antidepressant

TBI- Traumatic brain injury

ACTH- Adrenocorticotropic hormone

ERP- Exposure response prevention

CBT- Cognitive behavioral therapy

DSM-IV- Diagnostic and Statistical manual of mental disorder

COPD- Chronic obstructive pulmonary disease.

Table 1: Dosage and therapeutic level of drugs for Schizophrenia ^39,40,41

 

Class/subclass	Brand name	Daily dose range usually reported in literature (mg/day)	Standard initial dose range for young, healthy patients (mg/day)
Butyrophenones (haloperidol)	Haldol	2-30	4-8
Phenolindole (sertindole)	Serlect	12-24	4-8
Dibenzothiazepine (quetiapine)	Seroquel	300-500	50-100
Dibenzodiazepine (clozapine)	Clozaril	75-800	25
Benzisoxazole (risperidone)	Risperdal	1-10	2-4
Benzisothiazolyl piperazine (ziprasidone)	Geodon	80-160	80

Table 2: Nonstandard adjunctive treatments for schizophrenia ⁴²

 

Proposed agent	Usual dose range (added to antipsychotic)	Strength of evidence
ECT	Up to 12 treatments	Moderate
Lithium	Dose to obtained level of 0.6-1mEq/L	Moderate
Carbamazepine	Dose to obtained level of 6-12mcg/ml	Weak
Famotidine	40mg/day	Weak
Ondansetron	1mg b.i.d	Weak
Cycloserine	50mg/day	Modest

Table 3: Medication associated with depression

Drug category	Proposed agent
Anticonvulsants	Phenobarbitol, clonazepam
Antihypertensive	Reserpine, clonidine, α-methyaldopa
β-blockers	Propanalol
Steroids	ACTH, glucocorticoids
Histamine blockers	Cimetidine, ranitidine
Drugs	Cocaine, amphetamine, alcohol
Others	Ethanbutol, levodopa, cycloserine

Table 4: Alternative augmentation strategies for depression

Medication	Dosage
Pergolide	0.05-1 mg/day for 1 week
Estrogen	0.125-0.375 mg/day for 2 weeks
Sodium valproate	750-1500 mg/day for 3 weeks
Carbamazepine	600-1200 mg/day for 3 weeks
Pindolol	7.5-15 mg/day for 1 weeks
Buspirone	30 mg/day for 3 weeks
Modafinil	200-400 mg/day for 1 weeks

Figure 1: An algorithm for the treatment of bipolar disorder 43

About Authors:

Shrivastava S
Lecturer, Smriti College of Pharmaceutical Education, 4/1, Pipliya Kumar Kakad Mayakhedi Road, Indore (M.P.) 452001, India, Tel: +91-731-2802262, Fax: +91-731-2802467, E-mail: satyaendrascope@gmail.com

Dubey D
Lecturer, Smriti College of Pharmaceutical Education, 4/1, Pipliya Kumar Kakad Mayakhedi Road, Indore (M.P.) 52001, India. Tel: +91-731-2802262, Fax: +91-731-2802467 , E-mail: darshandubey@gmail.com

Dubey P.K.
Principal, Swami Vivekanand College of Pharmacy, Khandwa Road, Near Toll Naka, Indore (MP) 452020, India Tel: +91-731-3096144, E-mail: pkdubeysvcp@rediffmail.com

Kapoor S
Lecturer, Smriti College of Pharmaceutical Education, 4/1, Pipliya Kumar Kakad Mayakhedi Road, Indore (M.P.) 452001, India