Psychotic (Delusional) Depression

The primary classification system for diagnostic classification in psychiatry is currently the Diagnostic and Statistical Manual of Mental Disorders , 5th edition (DSM5) of the American Psychiatric Association. Although psychotic major depression is simply classified as a severe form of major depression in DSM5, psychotic major depression may represent a unique subtype of melancholic major depression with its own phenomenology, treatment response, and biology. The course of major depression is predominantly chronic (although the melancholic subtype is typically acute), with considerable treatment resistance, and depression is estimated to be the leading cause of disability in the year 2030. Psychotic features occur in about 14% to 25% of patients with major depression. Psychotic major depression may be associated with an especially chronic course, more frequent hospitalizations, higher risk of suicide, and greater disability than other forms of depression.

In DSM5, psychotic symptoms, delusions, and hallucinations may be classified as congruent (delusions of guilt, ruin, nihilism, hypochondria, or derogatory or accusatory hallucinations) or incongruent with mood (persecutory delusions, self-referral, control, or hallucinations without affective content). In psychotic depression, usually people have extraordinary delusions that they are worthless to society, guilty of horrifying crimes, undeserving of life, that their body is physically rotting away, and even that they are already dead (diagnosed as Cotard syndrome).

The prevalence of depressive disorder with psychotic symptoms has been investigated in population studies. According to one US study, the prevalence of psychotic symptoms was about 14% among patients with major depression. In a multicenter study conducted in Europe, the prevalence of psychotic symptoms in major depressive episodes was 18.5% and in the general population, 0.4%. Another epidemiologic study in the UK found an incidence of psychotic depression similar to that of schizophrenia. The presence of psychosis is greater in severe depressive episodes, but is also found in mild to moderate conditions. Psychotic (delusional) depression is considered a severe form of melancholia.

Melancholia

In DSM5, melancholia is only a specifier of major depressive disorder. Melancholic depression, or depression with melancholic features, is a DSM5 subtype of clinical depression ( Table 6.1 ). According to DSM5, melancholic features apply to an episode of depression that occurs as part of either major depressive disorder or bipolar disorder ( Table 6.2 ).

Melancholia: Secondary Signs and Symptoms

Melancholia is characterized by a severe episode of sad or apprehensive, nonremessive, and nonreactive mood, with acute onset, for a period of at least 2 weeks and impairment of the individual’s daily activities. Melancholia also includes changes in psychomotor activity and vegetative symptoms, besides the possibility of psychotic symptoms. The main characteristics that separate melancholic depression from non-melancholic depression are psychomotor retardation, pervasive sad mood, lack of reactivity, and lack of interest. Psychomotor retardation and delusional symptoms are cardinal symptoms in this distinction.

Other clinical differences are also described; those with melancholia are more likely to report such clinical features as anhedonia and anergy than those with lesser depressions. The condition is associated with a seemingly lower importance of stressful life events, lower rates of personality disorders, lower family history of alcoholism, and higher rates of suicide when compared with non-melancholic depression. Likewise, there is evidence for differential response to treatment: there are many studies suggesting a diminished response of melancholia to psychotherapy, and a superior response to antidepressant medication.

Even with somewhat varying clinical definitions, melancholic depression has been held to differ from non-melancholic depression across a number of biological parameters. These differences include (a) genetic: with an association of the melancholic subtype and the long allele of the serotonin transporter gene ; (b) biochemical: altered signal transduction in fibroblasts ; (c) anatomic: reduction of hippocampal volume ; (d) endocrine: an increased rate of dexamethasone nonsuppression ; and (e) circadian rhythm: as measured by polysomnography.

Melancholia and Psychosis: A Continuum?

Mehl et al. reported that persecutory delusions were independently predicted by personalizing bias for negative events and by depression in 258 patients diagnosed with schizophrenia. Some investigations indicate that persecutory delusions are associated with abnormal attention to threat-related stimuli: an explanatory bias toward attributing negative outcomes to external causes and biases in information processing relating to self-concept. It is hypothesized that in delusional patients, activation of self-discrepancies by threat-related information triggers defensive explanatory biases, which have the function of reducing the self-blame, but lead instead to persecutory ideation. Symptoms such as purposelessness are common in melancholia and delusional depression, and might be related to diminished coping and psychotic experience. The delusions and hallucinations may both cause or reflect greater psychological distress, such as the obsessional guilt and perceived victimization common to delusional depression.

Mild Psychosis-like Features in “Nonpsychotic” Cases

A comprehensive list of clinical features confirmed that “nonpsychotic” melancholia cases evidenced greater psychomotor change, and while they reported a more severe mood disturbance, it was distinguished more by sustained duration than by severity. However, they were no more likely to report greater numbers of vegetative features (e.g., appetite or weight change, insomnia). Additionally, both constipation and an absence of diurnal variation in mood were more likely to be reported by nonpsychotic subjects.

Prepsychotic Onset Comorbidity

Melancholia is an acute syndrome. However, in a significant number of cases we find a certain general type of personality and habits of life. A review of the patient’s previous personality and temperament often show that he/she has been an inhibited type of individual with a tendency to seriousness, rigidity, humorlessness, and over-conscientiousness. Daily life habits have been narrowly focused, somewhat stereotyped, and devoid of diversions. Frequently he/she has been a loyal subordinate, meticulous with details, rather than an aggressive leader. The narrow range of interests, modest adjustment skills, asocial trends, inability to maintain friendships, intolerance, and sometimes middling adult sexual adjustment are frequent personality concomitants. Likewise, there may be a rigid ethical code, proclivity for saving, profound reserve, significant sensitivity, outward evidence of anxiety, over-conscientiousness, and the meticulousness about relationships and work.

Fictional Case History

IDENTIFICATION: Anne, 62 years old, female, white, owner and headmaster of a private school.

CHIEF COMPLAINT: “I do not want to live anymore.”

HISTORY OF THE CURRENT ILLNESS: Anne attended the psychiatric consultation reporting that she had been feeling discouraged, tearful, sad, and “angry with the people around her” for the past 6 months. It began about when her husband of 40 years died suddenly after years of progressive cardiac failure. Anne then had trouble keeping up with her work: “Doctor, I cannot do anything I did before. My life is misery, I am a worthless waste of biology.” The early and terminal insomnia as well as anorexia and progressive weight loss became a constant in her life. However, what others noted most was her newfound social isolation. Anne does not want to continue living, feels wronged by God, and thinks she is alone because of unhelpful coworkers and family.

As time passed, Anne became increasingly dysfunctional, restless, exhausted, and brooding. What sleep she had was easily disturbed and not at all refreshing. Anne forced herself to get out of bed, couldn’t concentrate, struggled to remember things, couldn’t make decisions, and became convinced of rapidly progressive dementia. Even though her staff saw that she was still able to effectively run the school despite her condition, she was convinced that her contribution was nonexistent, and the school, staff, and students would be better off without her.

Upon psychiatric examination, Anne is severely inhibited psychomotorically, physically rigid, and without affective responsiveness. As she tries to cooperate, her facial expression is frozen, and there are long pauses as she tries to answer questions. She reports that she has lost the ability to rejoice or cry. Her most important themes include her fears of failing her school, overburdening her son, and altogether failing at her own purpose and existence. As fear of financial ruin becomes overwhelming, thoughts of a hopeless future turn into a fixed delusion of impending financial ruin, despite her financial assets. Finally, Anne is convinced that her inner organs are rotting away, and that the certainty of her imminent death would be a relief to everyone. She had no prior history of mania or other psychiatric diagnosis or treatment.

PERSONAL HISTORY: Born in Rio de Janeiro, Anne is the eldest of five children. Childhood psychomotor and cognitive development was within the normal range. She was raised only by her mother, and had no contact with her father. During her childhood she always felt alone, since “her brothers did not pay much attention to her.” Anne commented that as a shy child, she had few friends during childhood and adolescence, and limited social relationships with other relatives. Despite a strong education, she did not easily assimilate new ideas or adapt to new environments. Throughout her life, she was fastidious but conservative about personal appearance, and meticulous about the orderliness in her quarters. She presented personal thoughts from a pessimistic perspective, and considered herself a “perfectionist.” Anne had no stable romance until age 24, when she met Nathan, whom she married and with whom she had a son. Her husband was her pillar of strength. After his death, Anne continued to live in the same apartment. With her son working in Germany, she currently lives alone. In the midst of her overwhelming loss, she has few social resources to draw upon.

The Psychiatric Interview and Assessment

A main objective of the psychiatric interview is to establish the diagnostic hypothesis. This requires a thorough psychiatric evaluation and differential diagnosis, including comorbidities. For severe depression or first-episode psychosis, interview data must include current illness and prior illness signs and symptoms (including bipolar mania), disease onset, severity, and evolution. Information about personal history should include pre-morbid functioning, life events, stressors, and medical illnesses that might be related to the present illness.

This initial assessment should be viewed as a process for precise syndromal diagnosis, with attention to potentially causal medical conditions, including neurologic disorders and psychoactive substances use. The psychiatrist, when facing a first psychotic episode, must always investigate the possibility of a general medical condition, especially when patient or family report occurrence of physical signs and symptoms during or immediately prior to psychiatric manifestations, atypical psychiatric manifestations, later age at onset, or poor response to initial treatment.

At the same time, keep in mind that true melancholic and delusional depressions are often triggered by serious medical illness. In DSM5, unipolar major depression with psychotic features is a severe subtype of unipolar major depression. Psychotic symptoms of delusions and/or hallucinations are usually consistent with depressive themes of guilt, worthlessness, and ruin.

Besides clinical history and medical review of systems, laboratory tests are useful for detecting some medical conditions. Commonly used tests examine: complete blood count; fasting glycemic level; electrolytes; autoimmune diseases; HIV and syphilis serology; and kidney, liver, and thyroid function. Computed tomography or magnetic resonance imaging help to detect brain injury, and are especially important in the presence of neurologic signs and symptoms, atypical presentations of psychosis, symptoms suggestive of delirium, and in patients over 50 years of age. All abnormalities should be followed up in concert with appropriate medical specialists, but do not automatically preclude psychiatric diagnosis.

Some basic guidelines for interviewing acutely psychotic patients are included near the end of Chapter 1 .

The Melancholic Patient’s Interview

On interview, a severely depressed patient may have impaired concentration, anergia, diminished motivation, and psychotic preoccupation, and thus provide very little information. Since the interview will often be shorter than usual, it may be best to avoid too many open-ended questions and focus instead on specific and direct questions. Interventions that reflect empathy for patients’ perceived despair, hopelessness, low self-esteem, and future prospects may improve the quality of the interview data. For suicide risk assessment, it is essential to pose direct questions about ideation, plans, and previous attempts in this high-risk group. However, since the most suicidal patients may offer no direct confirmation of their thoughts and plans, it is also essential to listen for risk with a third ear. Similarly, many will hesitate to disclose delusions and hallucinations.

If some topics cause patient discomfort, a brief detour to more neutral topics may help. As a rule, start with more positive topics, then move to neutral areas, and finally to those that are more emotionally charged. In looking for positive aspects of the patient’s current perspective, you can say: “Tell me what you appreciate about yourself.” When feelings or cognitions require clarification or elaboration, you can say: “What did you feel at that moment?” or “What went through your mind?”

If patients hint at delusional themes during the initial interview, this presents an opportunity to return to that theme later for elaboration. Eventually, the interview should explicitly ask about possible delusional concerns. Those concerns generally reflect a severely pessimistic view of life, guilt, health, financial status, and related human concerns and fears. The delusional nature of those thoughts is determined by the degree of conviction, uncorrectability, dismissal of contrary evidence, and any resulting relevance for action or resolute passivity. As melancholic and delusional thoughts drive away hope, the future becomes increasingly hopeless and frightening. The delusional fear of suffering from an incurable physical disease is supported by perceived physical heaviness and lassitude, vegetative changes, out-of-body experiences, and depersonalization. Patients can experience these internal physical symptoms as proof of hopeless illness, and will sometimes even convince family and other physicians that they can never recover.

Patients who are primarily focused on their interpersonal relationships and responsibilities are increasingly concerned about their depressive inhibition and concerns about their failure to fulfill their personal obligations. Fears of failing, burdening, or hurting a spouse, children, or family or of having harmed them in the past lead to delusions of guilt. For the religious faithful, failure begets delusions of sin before God. These processes can lead to nihilistic preoccupation with suicide.

Moments of temporary silence during the interview may evoke some patient anxiety, but also allow reflection and thus greater openness about topics under discussion. Silences may also reflect patient apprehension about a difficult issue—due to guilt, fear, mistrust, deliberate omission, or simply resistance.

Prolonged silences should be avoided, as they can lead to a break in interview communication and patient (or physician) resentment. Without waiting too long, say: “I realize that it is difficult to speak…” It is also important to remember that patients with severe depression may be stuporous, or even mute. In these cases, silence may represent a symptom of the psychopathologic picture that the patient presents.

Tools to Screen for Psychotic Depressive Patients

Some tools are available to help screen for psychotic depression. For instance, the Psychotic Depression Assessment Scale (PDAS), the Brief Psychiatric Rating (BPRS-5) subscale of the PDAS, and the Calgary Depression Scale for Schizophrenia (CDSS) may be used to assess psychotic depression. Specifically designed for individuals with schizophrenia, the Calgary Depression Rating Scale was originally developed to address the issue of the overlap between depression and negative symptoms and has become the recommended scale to assess the severity of depression in schizophrenia.

Results of these assessments might be biased by patient feelings of despair, hopelessness, low self-esteem, and pessimism about themselves, the world around them, and their future. In addition, patients with psychotic depression may have profound cognitive impairment. For example, one study showed that delusional depression is accompanied by deficits in visual memory, visuo-constructive abilities, speed of cognitive processing, and executive functions—all of which could make screening tools problematic. Furthermore, delusional depressive patients might have increased mistrust, leading to evasive answers and avoidance of eye contact.

Case Report Part II: Treatment

With diagnosis of a currently severe depressive episode with psychotic symptoms, Anne begins medication treatment with lorazepam 0.5 mg two times a day as a fixed-dose anxiety medication and Zopiclon 7.5 mg as a sleeping pill. Most importantly, perphenazine 8 mg four times a day is used as an antipsychotic, and amitriptyline 150 mg daily is used as an antidepressant.

Benzodiazepines offer some initial reduction of pessimism, as well as improved sleep duration. Anne’s son, in family counseling, confirms that Anne’s business is organized and financially sound. Psychomotor inhibition slowly improves over the course of treatment. Perphenazine starts a gradual reduction in delusions, and they eventually fade to unimportance. When the amitriptyline starts to work in the fourth week of treatment, sleep duration, appetite, and psychomotor function return to normal. Depressed mood gradually fades away, and some joy later returns. Lorazepam is reduced and later discontinued. Anne retains slight residual symptoms in the form of increased irritability, exhaustibility, and reduced resilience. She will continue treatment in an outpatient clinic during her further recovery.

Suicide Risk Assessment

Patients with melancholia have an increased risk of suicide compared to the general population. Investigations demonstrated that patients with depression with melancholic features had a greater prevalence of suicidal ideation. Furthermore, patients with delusional depression are at a two-fold higher risk, both during their lifetime and in the acute phase, of committing a suicidal attempt than patients with non-delusional depression. There were no differences in suicidal tendencies between mood-congruent and mood-incongruent psychotic depressive patients. Delusional depression patients have a significantly higher level of violent suicide attempts. Furthermore, patients with delusional depression committed more severe suicidal attempts when compared with non-delusional depressive patients. Similarly, psychological autopsy of completed suicides found that psychotically depressive patients more frequently used violent methods than their non-psychotically ill counterparts.

It is not clear why the presence of psychotic features should be associated with this increased suicidal risk in delusional depressive patients. Many factors have been suggested. The association of psychosis with depression is often associated with an overall greater depression severity, which might contribute to higher levels of suicide attempts. However, there are also reports that when delusional depressive and non-delusional depressive patients suffered from depressive episodes of equal severity, the delusional depressive group still had higher levels of suicide attempts. Most likely, then, this elevated risk might more likely be due to psychosis per se (e.g., command hallucinations, delusional ideas), pronounced guilt feelings, impulsivity, or greater executive dysfunction (closely linked with psychosis), which interferes with rational problem-solving abilities. Additionally, delusional depression’s higher levels of psychomotor disturbance (i.e., agitation) and longer duration of depressive symptoms might play a role in increasing the rate of suicide attempts. Detailed and thoughtful suicide risk assessment is imperative with melancholic or delusional depression patients, along with effective treatment and suicide risk management plans. Even when no suicide risk is elicited, hospitalization should still be carefully considered for delusional depression.

Diagnostic Syndrome

Delusional depression is commonly regarded as a psychotic form of melancholic depression, despite DSM5’s inclination to lump many forms of depression together as major depression. Importantly, melancholia presents a distinctive biological homogeneity in clinical experience and laboratory markers and is differentially responsive to specific treatment interventions. Melancholia has characteristic clinical features, including:

• 1.
  

  Psychomotor disturbance expressed as retardation or as spontaneous agitation.

  
  
• 2.
  

  Disturbances in affect disproportionate to stressors, marked by blunted emotional response, and nonreactive mood.

  
  
• 3.
  

  Reduced concentration.

  
  
• 4.
  

  Vegetative dysfunction manifested as interrupted sleep, loss of appetite and weight, reduced libido, and complaints about low energy, especially in the morning.

  
  
• 5.
  

  Although psychosis is not necessarily a feature of melancholia, it is often present. Nihilistic convictions of hopelessness, guilt, sin, ruin, or disease are common psychotic themes.

Several biological markers are frequently found in melancholic patients compared to other forms of depressive illness:

• 1.
  

  Hypercortisolemia is common in melancholia and relatively uncommon in non-melancholic mood disorders. The hypercortisolemia is demonstrated in the dexamethasone suppression test. Hypercortisolemia and its failure to be suppressed by exogenous steroid administration is characteristic of patients with melancholia, and studies have demonstrated that this abnormality is normalized with effective electroconvulsive therapy. Interestingly, similar cortisol abnormalities seem to cause death in spawning salmon, and in two species of newly mated male marsupial mice. A return of the abnormality after treatment cessation heralds relapse of the disorder. However, clinical use of the DST for melancholia faded when studies of DSM-III major depression found little value for that more broadly defined diagnosis.

  
  
• 2.
  

  Psychomotor disturbances can include physical retardation, including immobility, slumped posture, slower movement, and muteness.

  
  
• 3.
  

  Characteristic disturbances in sleep architecture, with reduced rapid eye movement (REM) latency, increased REM time, and reduced deep sleep.

  
  
• 4.
  

  Markers of inflammation implicated in depression were quantified as higher in melancholic patients compared to non-melancholic patients. In pursuing an autoimmune contribution, melancholic patients were more likely to test positive for a 5-hydroxy-tryptophan antibody compared to non-melancholic and control participants.

  
  
• 5.
  

  Low plasma serotonin level predisposes to melancholia.

  
  
• 6.
  

  Neuroanatomically, melancholic patients had less gray matter volume in the left posterior insula and more white matter volume in the upper brainstem tegmentum compared to controls, less overall gray matter volume compared to controls, and evidenced more EEG abnormalities during consummatory reward tasks.

  
  
• 7.
  

  Clinical genetic studies suggest a familial aggregation and a considerable heritability of psychotic depression partly shared with schizoaffective disorder, schizophrenia, and affective disorders. Molecular genetic studies point to potential risk loci of psychotic depression shared with schizoaffective disorder, depression, bipolar disorder, and schizophrenia (6p, 8p22, 10p13-12, 10p14, 13q13-14, 13q32, 18p, 22q11-13) and several vulnerability genes possibly contributing to an increased risk of psychotic symptoms in depression (e.g., BDNF , DBH , DTNBP1 , DRD2 , DRD4 , GSK-3beta , MAO-A ). The 5- HTT , DTNBP1, and TPH1 gene variation are implicated in pharmacogenetic investigations, and in the mediation of antidepressant treatment response in psychotic depression. Genetic factors are suggested to contribute to the disease risk of psychotic depression in partial overlap with disorders along the affective-psychotic spectrum. The transition from nonpsychotic depressive disorder to a psychotic form is more likely to occur in patients with genetic markers for frontal cortex hypofrontality or increased dopaminergic activity.

Future research should be performed in order to identify specific melancholia characteristics. Increased research on this serious and debilitating disorder is important, so that melancholia be better recognized as a distinct, identifiable, and specifically treatable affective syndrome.

Summary

Melancholia is a lifetime diagnosis, typically with recurrent episodes. Within the present classification it is frequently seen in severely ill patients with major depression and with bipolar disorder. Therefore, a detailed interview assessing suicide risk and presence of delusions and hallucinations is important to help the physician in melancholia’s diagnostic and in the patient’s treatment. Hypercortisolemia (reflected in the dexamethasone suppression test), disturbances in sleep architecture, and other biological characteristics of melancholic patients should be further evaluated. Therefore it is important that future diagnostic manuals classify melancholia and delusional depression as distinct, identifiable, and treatable affective syndromes, rather than as just specifiers within major depression. This would reduce the odds that these conditions will be underdiagnosed and underreported by physicians, and allow improved treatment for these debilitating disorders.