We’ve seen in the Geddes Systematic Overview and Meta-Regression Analysis from the year 2000 how the second generation “Atypical” Antipsychotic drugs have proven:
"
Conclusions There is no clear evidence that atypicalantipsychotics are more effective or are better toleratedthan conventional antipsychotics."
We've seen how Psychiatric Diagnosis and drug treatment for the 100% Junk Fabrication/Diagnosis of ADHD Leads to ever escalating Severity of Additional Psychiatric Diagnosis and Drugs.
We’ve Seen just what type of Elected Nitwits have Authorized the Unlawful Industry of Psychiatric Interventions:
Allen Jones Full Whistle-Blower Report, pg.3.
"Newspaper columnist Charles T. Bowen, in an article "Quick Note; Silent Vote; No Gloat."
The Tampa Tribune, 21 April 1997, described how one former Texas legislator, Tom Robbins, was annoyed that his colleagues seemed to pass legislation that they had not even read, let alone understood. To prove a point he introduced a resolution to honor Albert de Salvo. The language of the resolution stated in part:
"Newspaper columnist Charles T. Bowen, in an article "Quick Note; Silent Vote; No Gloat."
The Tampa Tribune, 21 April 1997, described how one former Texas legislator, Tom Robbins, was annoyed that his colleagues seemed to pass legislation that they had not even read, let alone understood. To prove a point he introduced a resolution to honor Albert de Salvo. The language of the resolution stated in part:
"This compassionate gentleman's dedication and devotion to his work has enabled the weak and the lonely throughout the nation to achieve and maintain a new degree of concern for their future. He has been officially recognized by the state of Massachusetts for his noted activities and unconventional techniques involving population control and applied psychology."
The Resolution passed with a unanimous vote.
Albert de Salvo was, of course, the Boston Strangler.
The Illness Postulators plying the Psychiatric Con are empowered By State Governments like the above Boston Strangler’s applied psychology praisers to inflict what’s called an Industry Recognized “Standard Of Care”. Since the New antipsychotics are No Better – (and in some areas are considerably Worse) -
(And in San Francisco DPH Formulary Documents J&J’s Atypical Risperdal costs 31.67 Times More than the older Typical antipsychotic haloperidol (Haldol).
than the Old antipsychotics which formerly constituted the "Standard Of Care" (along with electrocutions and surgical lobotomies), ..... let's look at the Older Drugs to understand What it is that the Newer drugs are WORSE than.
There’s always been this disturbing effect – the one that causes Murders & Suicides – called Akathisia which is a part and inseperable parcel of making people ‘Mentally Healthy’ by poisoning them with derivatives of Industrial Dyes & Insecticides.
psychrights.org makes available:
Theodore Van Putten, M.D., and Stephen R. Marder, M.D.
J Clinical Psychiatry 48:9 (Suppl), September 1987
Here's the - to us - 2 Most Disturbing sections of this paper:
"In the haloperidol group, 17 (40%) of 44 patients experienced akathisia within the first 6 hours after the 5-mg test dose. Further, this akathisia was not mild or inconsequential. Of those patients who experienced akathisia during the first six hours after taking a 5-mg tablet of haloperidol, five (25%) experienced moderate, three (17%) experienced severe, and four (22%) experienced very severe akathisia. During the initial week of treatment with haloperidol (10 mg at bedtime), progressively more patients experienced akathisia; by the seventh day of treatment, 31 (76%) had experienced akathisia."And:"The unreplicated work of Van Putten and associates (5, 53) does not imply that antipsychotic drugs should be withheld from patients with a dysphoric response. Some patients with a dysphoric response eventually make peace with antipsychotic medication and experience good symptomatic improvement – often, in our experience, with very low doses, e.g., thioridazine 50 mg/day or fluphenazine decanoate 5 mg i.m. every 2 weeks. Others experience fair symptomatic improvement at the expense of ongoing dysphoria. If such persons are floridly psychotic and dangerous to others in an unmedicated state, then their dysphoria in a medicated state is clearly a worthwhile trade-off."
OK: We've got 76% Akathisia _ with people wanting to jump right out of their skin - by the seventh day of treatment, followed by the Jaw Dropping;
"If such persons are floridly psychotic and dangerous to others in an unmedicated state, then their dysphoria in a medicated state is clearly a worthwhile trade-off."
76% Akathisia, and slugging them into a "I dunno & I don't Care" at the Same Time, is clearly a Worthwhile Trade Off?"
And you Wonder why, people who've been run through This mill are presented by our "Hit & Run" Media/Boston Strangler Praising Legislatures as being a Danger to others?
And to Cap the Entire Fiasco off: None of it Works, At ALL!
The Largest Chain Hospital Organization in the World - the United States Veterans Administration - Admits, that the program/drugs are Not Working:
"Though a positive outcome has not been observed with the NJ Algorithm to date, ....."
Theodore Van Putten, M.D., and Stephen R. Marder, M.D.
J Clinical Psychiatry 48:9 (Suppl), September 1987
Extrapyramidal symptoms cause much misery, often go undiagnosed, and can interfere with treatment and rehabilitation. Akinesia is a behavioral state of diminished motoric and psychic spontaneity that is difficult to distinguish from the negative symptoms of schizophrenia. The most useful clinical correlates of clinical akinesia are a subjective sense of sedation and excessive sleeping. Akinesia interferes with social adjustment and may manifest as “postpsychotic depression.” The subjective restlessness of akathisia is usually accompanied by telltale foot movements: rocking from foot to foot while standing or rocking on the spot. Akathisia is strongly associated with depression and dysphoric responses to neuroleptics and has even been linked to suicidal and homicidal behavior in extreme cases.
(J. Clinical Psychiatry 48 [9 Suppl]: 13-10, 1987)
Over the past decade our work has indicated that extrapyramidal symptoms cause much misery, often go undiagnosed, and can interfere with treatment and rehabilitation. However they remain a controversial and ill-studied area in which there are many assertions and dramatic case reports. Part of the problem is that the measurement of extrapyramidal symptoms is in a primitive state.
Tardive dyskinesia is characterized by observable involuntary movements and usually can be measured adequately – both in clinical practice and in research – with rating scales such as the Abnormal Involuntary Movement Scale (AIMS). (1) Dystonic reactions are similarly observable, but more subjective and intermittent dystonic reactions such as intermittent leg cramps, a tightening of the jaw, cramps of the abdominal wall muscles, or intermittent neck discomfort are often not regarded as dystonic. When dystonic reactions are intermittent they may be regarded as “hysterical”. The diagnosis of akinesia and akathisia, however, is in a primitive state.
AKATHISIA
Akakthisia is often difficult to diagnose. In severely thought disordered, agitated patients, the distinction between akathisia and psychotic excitement may be impossible. At the other extreme, it may be very difficult to distinguish vague anxiety or emotional unease from akathisia. The lack of precise diagnostic criteria may be related to the dual nature of akathisia: a subjective or psychological experience of restlessness and observable motor restlessness. Investigators disagree about the relative importance of these two aspects.
Our group, as is the custom in the United States, has diagnosed akathisia primarily by the patient’s responses to structured questions about inner restlessness and by response to antiparkinson drugs. Thus, we ask questions to which nearly all patients can respond intelligibly, such as “Do you fell restless or jittery inside?” and “Is it difficult to sit still?” Amelioration of the reported restless state with the usual antiparkinson medications then confirms the diagnosis.
The British (2), however, have rightly stated that akathisia cannot be reliably diagnosed by the patient’s subjective report. We agree with Barnes and Braude (2) that “general complaints of emotional unease” or “Inner restlessness” are too non specific for a diagnosis of akathisia. Barnes and Braude have added the more observable criteria of restless leg movements. They claim to distinguish “between patterns of normal restless leg movement and abnormal (dyskinetic) movements. We, however, are unable to distinguish in a great number of cases between those “purposeless” and “fidgety” movements of the upper and lower extremities that are normal, restless, or dyskinetic, and we doubt that others can.
We proposed that the restless movements of akathisia be confined to those foot movements that all clinicians are familiar with: rocking from foot to foot while standing or walking on the spot. These foot movements are easily recognized and, in our experience, are present in all patients with moderate or severe akathisia. Barnes and Braude (2) agreed.
Barnes and Braude also agreed that mild akathisia may not be manifested in observable movements (particularly if the patient has coexisting akinesia). This subjective state can, nevertheless, be tormenting (5,6,7) and may affect the course of treatment (7,8). A reasonable criterion for “subjective akathisia” is an experience of restlessness relieved to some degree by antiparkinson medication.
We realize that “subjective akathisia” cannot always be reliably differentiated from subtler psychotic excitement or a host of pathologic emotions. Nevertheless, the state, as any clinician will attest, does exist.
The Subjective Experience Of Akathisia
Patients with akathisia may describe vague feelings of inner tension, emotional unease, or anxiety, using such phrases as “all wound up like a spring,” “nervous-like,” a “hurry up feeling,” “unable to feel comfortable in any position,” “tense,” feeling like I have to do something,” “rowdy-like,” “an impatient feeling,” “irritable,” keyed up or wired up,” or “like jumping out of my skin.” Kalinowsky stated that akathisia can be “more difficult to endure than any of the symptoms for which … [the patient] was originally treated” and cautioned that it may be mistaken for “agitated depression.”
It may be useful to describe how akathisia was experienced in some of our more extreme cases. A 24 year old woman began to cry 3 hours after taking a 12 mg test dose of thiothixene hydrochloride. She felt that she was at her “wit’s end,” and when asked about restlessness, she answered that she was “miserable with a jittery feeling.” She began hearing voices urging her to leave the hospital, and she developed such strange behaviors as climbing the bookcases and crawling. An antiparkinson drug markedly alleviated the akathisia, the associated dysphoria, and the strange behavior. A 31-year old man, 3 hours after taking a 16-mg test dose of thiothixene hydrochloride, said he had “never felt worse.” He stated: “The voices have changed; they now say I’m going to die because I’ve taken the medication.” In his rambling words “death” and “dying” became frequent. When asked about restlessness, he spoke of an “inner queasiness.” An antiparkinson drug improved the akathisia and associated dysphoria. Other patients equated their akathisia with “that awful feeling” or “the worst misery.” Even if we allow for a certain amount of histrionic exaggeration, these experiences and behaviors are very similar to what normal subjects experience when they are given a high potency antipsychotic drug.
At times, akathisia can be associated with dramatic exacerbations of psychosis, (13, 14) an occurrence that probably depends on the meaning and significance that a psychotic mind attaches to the experience of akathisia. In extreme cases, akathisia is thought to have triggered (or caused) suicidal (15, 17) and even homicidal behavior (18, 20). Shaw et. Al. (20) reported the case of a 43-year-old-male paranoid schizophrenic patient who was switched under blind conditions from BW-234-U (a neuroleptic without extrapyramidal symptoms), to haloperidol, and back to the experimental drug. Self-report, spouse report, and blind objective clinical ratings indicated rapid clinical decline during haloperidol treatment that included moderately severe akathisia, suicidal and homicidal ideation, increased paranoia, and intensified anxiety, tension, and agitation. Keckich (18) reported a 29-year-old man with a predisposition to violence who, while receiving haloperidol 4 mg h.s. experienced akathisia and “violent urges to assault anyone near him.” These feelings culminated in an assault on his dog with an intent to kill. Schulte (19) reported a 23-year-old psychotic man with a predisposition to violence who, 1 to 2 hours after an injection of 10 mg of haloperidol in an emergency room, went on a rampage during which he murdered and maimed several people. This patient described severe extrapyramidal symptoms of an akathetic nature that were, in his words, the “determining factor.” Schulte described four other patients in whom akathisia was thought to have triggered (or caused) suicide (by hanging or by severe self-inflicted stab wounds of the abdomen) and two patients who committed severe homicidal assaults. Shear et al. (16) reported two violent suicides (jumping off a building and jumping in front of a subway train) attributed to unrelieved akathisia after injections of depot fluphenazine. Drake and Ehrlich (15) reported two cases of impulsive suicide attempts associated with akathisia in which suicidal ideation appeared suddenly, concurrent with neuroleptic induced akathisia, and disappeared when the akathisia was treated. Other reports of the pre-suicidal state of schizophrenic patients suggest that akathisia may have been a factor in precipitating suicidal behavior. Planansky and Johnston (21) reported that 70% of 52 schizophrenic subjects who had made suicide attempts showed “restlessness, pacing, irritability, tension, apprehension with delusional fears, and severe psychomotor upset” at the time of the attempts. Faberow at al. (22) described 30 schizophrenic subjects before they completed suicide as “extremely tense, restless, and impulsive. They made many requests or demands that something be done to relieve their tensions ….. They appeared driven to find some kind of relief.”
The aforementioned case literature reads convincingly: it is reasonable to conclude that akathisia, in the extreme case, can drive people to suicide or homicide.
Incidence Of Akathisia
Little is known about the incidence of akathisia because, to our knowledge, no one has systematically attempted to measure it. We (21) reported a precise tally of akathisia in two groups of schizophrenic patients: one group was treated with haloperidol and the other was treated with thiothixene hydrochloride. The patients were newly admitted (or readmitted), drug-free (for at least two weeks, but usually several months) schizophrenic patients who were given an oral test dose of either haloperidol 5 mg or thiothixene hydrochloride 0.22 mg/kg. Following administration of the test dose, the patients were observed for 24 hours; thereafter, a fixed dose regimen of haloperidol 10 mg at bedtime or thiothixene 0.44 mg/kg at bedtime (mean dose ± SD = 28.5 g ± 8.6 mg) was continued.
In the haloperidol group, 17 (40%) of 44 patients experienced akathisia within the first 6 hours after the 5-mg test dose. Further, this akathisia was not mild or inconsequential. Of those patients who experienced akathisia during the first six hours after taking a 5-mg tablet of haloperidol, five (25%) experienced moderate, three (17%) experienced severe, and four (22%) experienced very severe akathisia. During the initial week of treatment with haloperidol (10 mg at bedtime), progressively more patients experienced akathisia; by the seventh day of treatment, 31 (76%) had experienced akathisia.
The incidence of akathisia with thiothixene was somewhat lower than that with haloperidol: 20% of 67 patients experienced akathisia 12 hours after taking a 0.22 mg/kg (0.1 mg/lb) test dose of thiothixene. However, 7 patients who had a dystonic reaction and were given an antiparkinson drug were excluded from the analysis on the assumption that the antiparkinson drug would prevent akathisia. (The inclusion of these 7 patients would have raised the cumulative percentage of patients with akathisia or dystonia to 28% within 24 hours of the administration of the first tablet of thiothixene.) During the next 4 weeks of treatment with a fixed dose of thiothixene (0.44 mg/kg or less), the cumulative percentage of patients with akathisia rose to 63%.
The high percentage of patients experiencing akathisia after taking even one dose of haloperidol ot thiothixene raises the question of whether it was the physician or the patient who was so sensitive to akathisia. The answer is neither: the reported incidence of side effects depended on how the side effect data were elicited. Reports of side effects were elicited with increasing frequency depending on whether one relies on spontaneous complaints, general questions (“How do you feel?”), or specific questions. For akathisia, we asked: “Do you feel restless or jittery inside?” “Is it difficult to sit still?” In addition, the physician was probably more sensitive to side effects. For example, if a patient mentioned feeling “strange,” “frightened,” or “weird,” the physician would first rule out akathisia by asking specific questions. In doubtful cases, amelioration by an antiparkinson drug would then support a diagnosis of akathisia.
We suspect that this high incidence of akathisia may also (at least in part) be a function of a sample of our rather calm and cooperative schizophrenics. It is commonly known that activated, excited patients (particularly those with schizoaffective disorder) can tolerate huge doses of neuroleptics. (24) Thus, the literature on rapid neuroleptization with haloperidol (24, 28) does not mention akathisia. There is, however, the unpleasant possibility that these studies may have overlooked akathisia because they relied on spontaneous complaints of akathisia and that excited schizophrenics with thought disorders are not readily capable of communicating their distress.
AKINESIA
Akinesia may be the most toxic behavioral side effect of antipsychotic drugs. It is defined by Rifkin et al. (29) as a “behavioral state of diminished spontaneity characterized by few gestures, unspontaneous speech and, particularly, apathy and difficulty with initiating usual activities.” As defined, this side effect often goes unrecognized.
It is notoriously difficult to differentiate schizophrenic apathy and blunting from akinesia. A measure that can distinguish between akinesia and the negative symptoms of schizophrenia or the psychomotor retardation of depression is needed. Constriction of handwriting (micrographia) is not a reliable correlate of akinesia (30); neither is antipsychotic drug or prolactin plasma level.. One useful correlate of akinesia, however, is a subjective sense of sedation. When rated at 9:00 a. m. (12 hours after h.s. dose) 88% of the akinetic patients rated themselves as slightly drowsy, as opposed to 18% of the non-akinetic patients. (5)
Leg crossing may be another useful correlate of akinesia. Most persons (except the very obese or tense) will cross their legs when seated in a comfortable chair; persons with Parkinson’s disease do not. (32) Figure 1 shows the relationship between severity of akinesia and leg crossing in 130 schizophrenic patients (as rated during an interview ranging from 5 to 20 minutes). Almost 80% of nonakinteic schizophrenic patients crossed their legs when seated in a comfortable chair, but only 10% of patients with mild akinesia crossed theirs. (33) Thus, if a schizophrenic patient does not cross his legs during a brief interview, there is a good chance that he is experiencing a drug induced akinesia.
The Experience Of Akinesia
Sacks (34) described encephalitic patients who were “awakened” from incapacitating parkinsonian akinesia with L-dopa when it was first introduced. These patients experienced akinesia as a peculiar thoughtless, emotionless, and will-less state. One patient had this to say about her years of akinetic immobility: “I have ceased to have any moods. I ceased to care about anything. Nothing moved me – not even the death of my parents. I forgot what it felt like to be happy or unhappy. Was it good or bad? It was neither. It was nothing.”
In the treatment of schizophrenic illness with neuroleptics, akinesia, in our experience, produces a type of improvement. The patient talks less of psychotic material, but he talks less of everything; he is less bothered by his hallucinations, but he is less bothered by everything else as well. Many patients with akinesia experience a peculiar absence of emotions, appear emotionally dead, and often state that everything is all right. This type of improvement, which occurs particularly with higher doses, is one that we should not be proud of.
Akinesia has been associated with improvement of psychosis and a deterioration in blunted affect, emotional withdrawal, and motor retardation. In a prospective study (35) of 76 newly admitted schizophrenic patients treated with haloperidol, the correlation between akinesia and the Brief Psychiatric Rating Scale (BPRS) factor was + .43 (p=.0001) and the correlation between akinesia and the BPRS schizophrenia factor was - .39 (p=.004; pooled within-subject correlations).
Some psychotic patients whose positive symptoms are only partially sensitive to neuroleptics can improve only if they have akinesia. When intractable positive symptoms are distressing (subjectively or to others), an akinetic dampening of the entire mental life is often desirable. In those whose positive symptoms are neuroleptic-sensitive, however, everything should be done to minimize akinesia because it is socially disabling.
Akinesia And Social Disability
Even mild akinesia is severely disabling. Akinetic apathy and lack of spontaneity are mistaken for the negative symptoms of schizophrenia and add to the notorious social and emotional disability of schizophrenic patients on maintenance therapy. The onus of detection is on the physician, for the patient seldom complains. Indeed, even when asked if he feels “slowed up” or “sluggish,” the patient often denies any difficulty and is seemingly locked in a peaceful, apathetic remoteness.
These are bold assertions, born more from clinical experience than controlled investigation. But there is some scientifically based evidence that akinesia has far-reaching consequences. Rifkin and Kane (36) studied 126 stable schizophrenic outpatients maintained on fluphenazine decanoate 12.5 mg every 2 weeks. Half of these patients were then randomly assigned to a 10% dilution (namely, 1.25-5 mg every 2 weeks). Stable low-dose patients reported better social adjustment than stable standard-dose patients, particularly in areas of role function. Family reports also indicated more satisfaction with stable low-dose than with stable standard-dose patients.
Poor social adjustment may well be one of the side effects of neuroleptics. Rifkin and Kane (36) speculate that the mechanism is akinesia: “ ….. akinesia should not be thought of as limited to a few neurological signs, such as diminished arm swing while walking, slow arm dropping, and slow gait, but should include complex behavior as well, such as social behavior. Since antiparkinson drugs were prescribed in their study, it is clear that antiparkinson drugs cannot be counted on to completely correct akinesia.
Incidence Of Akinesia
If akinesia is defined as a “behavioral state of diminished spontaneity characterized by few gestures, unspontaneous speech and, particularly, apathy and difficulty with initiating usual activities (29) (which we regard as the most useful definition) then the incidence is rather high. Rifkin and associates (37, 38) had to withdraw fluphenazine decanoate maintenance therapy from 35% of patients because of disabling akinesia, despite the use of a low dose (0.5 ml or 12.5 mg biweekly) and prophylactic procyclidine. In another study, Rifkin and associates (39) withdrew antiparkinson drugs from long term aftercare patients stabilized on antipsychotic drugs. After 3 weeks, 27% of patients receiving procyclidine placebo developed akinesia. The magnitude of these figures derived from raters sensitive to akinesia indicates that akinesia often goes undiagnosed.
We performed a study in which 76 newly admitted schizophrenic patients were randomly assigned to receive either 5, 10, or 20 mg of haloperidol for 4 weeks. The 5-mg and 10-mg dose groups experienced only minimal akinesia as long as they received antiparkinson drugs. Patients assigned to the 20-mg daily dose, however, experienced mild to moderate akinesia by the third and forth weeks of treatment in spite of antiparkinson drug treatment.
Akinesia And Post Psychotic Depression
Schizophrenic patients with postpsychotic depression have been described as “wooden” in appearance, 40 motorically “inactive or retarded,” lacking initiative to perform routine tasks, (41) experiencing overwhelming fatigue and neurasthenic symptoms, (42, 43) “hypersomnic,” and “emotionally withdrawn.”All of these symptoms, however, can be manifestations of akinesia induced by antipsychotic drug treatment. (2) Indeed, persons with Parkinson’s disease regularly experience “a blunting of interest and drive, amounting to apathy, a limitation in intellectual activity, and an apparent slowing of thought process and memory” (46) There is a high incidence of depression associated even with the early stages of parkinsonism, (47) and the depression of Parkinson’s disease seems out of proportion to the physical handicap. (48)
In one investigation, (49) 28 of 94 schizophrenic inpatients developed mild akinesia and 32 were free of extrapyramidal symptoms. Those who developed akinesia becames less psychotic, but they also experienced a significant, although modest, increase in depression ratings. Vigorous treatment of akinesia with trihexyphenidyl resulted in significant improvements in depression, somatic concern, anxiety, emotional withdrawal, blunted affect, and motor retardation as measured by both physicians’ and nurses’ ratings. A strong association between akinesia and both objectively rated and subjectively experienced sedative effect indicates that an “akinetic depression” is not likely if the patient does not look or feel drowsy. The 32 nonakinetic patients also became less psychotic, but not more depressed. Rifkin and associates, (37) in a maintenance study of remitted schizophrenics, also found that akinetic patients became significantly (although modestly) more depressed and withdrawn compared with their own baseline and with those who did not develop akinesia.
Some of the akinetic patients who did not become more depressed did experience dysphoria, stating that they felt “blah,” “listless,” or “tired” or that they had no “interest,” “life,” or “ambition.” However, they did not complain much and specifically denied sadness or depression; some of them seemed quite accepting of the dysphoric feelings. It appears that both the patient and the doctor can get used to a mild akinesia.
If an extrapyramidal symptom, particularly akinesia, is associated with depression (or if patients experience it as depression), then populations of schizophrenics stabilized with antiparkinson drugs should experience depression on withdrawal of the antiparkinson drug. This is so. In two different samples (one in Boston, (50) the other in Greece (51 52)) of chronic schizophrenic patients stabilized on antiparkinson drugs, sudden or gradual double-blind withdrawal of antiparkinson drugs resulted in increased anxiety, depression, and general dysphoria and suffering.
Table 1. Correlations in 105 Schizophrenic patients Between Subjective Response to Medication and Outcome, Both Measured at the Same Time*
_________________Pearson Product-Moment Correlation (r)
Group____________Doctor_____________Nurse______
Subjective_________Total______________Total_____Total_____
Response__________BPRS____CGI______MACC____NOSIE____CGI
Haloperidol (N=40)
___7 days_________.441_____.444_______.294_____.153_____.400
___28 days________.534_____.609_______.377_____.377_____.469
Thiothixene (N=65)
___48 hours_______.562________________.200________________
___28 days________.381_____.387_______.361_____.283_____.403
* Adapted from reference 53. Abbreviations: BPRS Brief Psychiatric Rating Scale, CGI=Clinical Global Impressions scale, MACC=Mack Behavior Adjustment Scale, NOSIE=Nurses’ Observation Scale for Inpatient Evaluation.
a p < .025
b p < .05
c p < .005
d p < .001
e p < .01
f One extreme outlier omitted (including outlier, r = .290, p < .05).
DYSPHORIC RESPONSES TO NEUROLEPTICS
Dysphoric responses to medication erode the quality of life. Lack of vigor, ever-present fatigue, lack of interest or motivation, muscular cramps and aches, inner restlessness or impatience, and vague complaints of “just not feeling right” are feeling states that schizophrenics often correctly attribute to their medications. Hogarty (Hogarty GE; personal communication, 1977) speaks of a “neuroleptic anguish” which, in his opinion, is poorly captured by conventional rating scales.
Even with moderate dosages and without gross side effects, a substantial minority of schizophrenic patients have a dysphoric response. These patients complain that the medication “keeps me closed in,” “Makes me feel spacey,” “takes me away from my normal frame of mind,” “slows my thinking,” “makes my whole body feel like it is in a physical prison,” or “makes me confused.” The majority of these dysphoric responders do not regard the medication as helpful.
To what degree are the patient’s and the professional’s perceptions of drug effect in agreement? The correlations between subjective response in two inpatient samples – one treated with haloperidol 10 mg/day, the other with thiothixene 0.44 mg/kg/day – and the doctors’ and nurses’ ratings of improvement are shown in table 1. (51) These correlations indicate a respectable agreement, both at the beginning and at the end of treatment, between subjective response and staff’s ratings of improvement – with two different drugs in two different samples. Stated another way, if the patient finds the medication helpful (a syntonic response), the staff’s ratings bear him out; conversely, patients with a dysphoric response are seen by the staff as doing less well.
Because many dysphoric responders (about 65% in both samples) stopped medication very early in their treatment course, we do not know whether they could have profited from antipsychotic medication. The dysphoric responders who completed 4 weeks of inpatient treatment tended to have a poorer outcome by both doctors’ and nurses’ criteria. (53)
The unreplicated work of Van Putten and associates (5, 53) does not imply that antipsychotic drugs should be withheld from patients with a dysphoric response. Some patients with a dysphoric response eventually make peace with antipsychotic medication and experience good symptomatic improvement – often, in our experience, with very low doses, e.g., thioridazine 50 mg/day or fluphenazine decanoate 5 mg i.m. every 2 weeks. Others experience fair symptomatic improvement at the expense of ongoing dysphoria. If such persons are floridly psychotic and dangerous to others in an unmedicated state, then their dysphoria in a medicated state is clearly a worthwhile trade-off.
In our experience, dysphoric responses to antipsychotic medication tend to be associated with extrapyramidal symptoms notably akathisia (5, 53) even with an antiparkinson drug, a persisting akathisia is not uncommon.
A PROSPECTIVE STUDY
In a recently completed prospective study (35) of 76 newly readmitted schizophrenic patients randomly assigned to receive haloperidol 5, 10, or 20 mg/day for 4 weeks, akathisia proved to be the most psychotoxic side effect. First, the patients with higher akathisia ratings dropped out of the study significantly more often. These drop outs talked only about leaving the hospital, and we believe this ideation to be a manifestation of akathisia. Second, the severity of akathisia was significantly related to the BPRS, both in individual patients, (r = .32; p = .0001) and across patients (r = .43; p = .0005). There were also substantial correlations between the severity of akathisia and the Symptom Checklist-90 (SCL-90) ratings (a rating scale that measures subjective distress). Third, in a prior study of outpatients by our laboratory we found significant relationships between akathisia and both depression and anxiety. We therefore regard akathisia as a substantial contributor to dysphoric feeling states in the usual, newly admitted patient treated with a conventional dose neuroleptic (haloperidol 10 or 20 mg/day) or the usual schizophrenic outpatient treated with fluphenazine decanoate in a dosage range of 5-25 mg bi-weekly. Since all patients with akathisia were treated with the usual antiparkinson drugs (usually benztropine up to 8 mg/day), it is really treatment resistant akathisia that caused the dysphoria.
In the prospective study (35) akinesia manifested itself behaviorally as blunted affect, emotional withdrawal, and motor retardation (akinesia vs. BPRS withdrawal-retardation factor, r = + .48 after 4 weeks of treatment). Kane et al. (54) in a maintainance study that compared fluphenazine dcanoate 1.25-5 mg with 12.5-50 mg every 2 weeks, also found statistically significant elevations in blunted affect, emotional withdrawal, tension, and motor retardation in the high-dose group. They too speculated that subtle drug-induced neuroleptic side effects (akinesia) accounted for those dosage effects.
Do the results of this prospective study invalidate prior findings (49) of “akinetic depression” and of akathisia causing psychotic decompensation? The answer is no. The patients with akinetic depression in the earlier work had a much more severe form of akinesia, but in 1978 we were not nearly as sensitive to the diagnosis of akinesia as we are now. Likewise, patients in the earlier studies had more severe akathisia. (In 1974, our patients were on higher doses of neuroleptic, usually fluphenazine decanoate, and they experienced much more severe akathisia, which was hardly recognized at that time.) Several patients did become dramatically worse as a result of intractable akathisia. One man experienced “explosions in my body” and became suicidally preoccupied; another man, mildly retarded, experienced “worms crawling on my bones.” Both men improved remarkably as the akathisia was controlled.
The chief problem with further research into akinesia and akathisia is our inability to measure these disorders exactly and uniformly from one center to the next. To overcome this deficiency, our laboratory is developing electronic hardware to measure extrapyramidal symptoms.
REFERENCES
- Guy W. ECDEU Assessment Manual for Psychopharmacology Rockville, Md, national Institute of Mental Health. Psychopharmacology Research Branch, 1976
- Barnes TRE, Braude WM: Akathisia variants and tardive dyskinesia. Arch Gen Psychiatry 42:874-878, 1985
- Van Putten T. Marer SR: Toward more reliable diagnosis of akathisia (letter). Arch Gen Psychiatry 43:1015-1016, 1986
- Barnes TRE, Braude WM: Toward more reliable diagnosis of akathisia (letter) Arch Gen Psychiatry 38:1016, 1986
- Van Putten T, May PRA, Marder SR, et al: Subjective response to antipsychotic drugs. Arch Gen Psychiatry 38:187-190, 1981
- Van Putten T, May PRA: The many faces of akathisia. Compr Psychiatry 16:43-47, 1975
- Van Putten T, May AQPRA: Subjective response as a predictor of outcome in pharmacotherapy: The consumer has a point. Arch Gen Psychiatry 35: 477-480, 1978
- Marder SR, Van Putten T, Mintz J, et al: Costs and benefits of two doses of fluphenazine. Arch Gen Psychiatry 41: 1025-1029, 1984
- Kalinowsky LB: Appraisal of the “tranquilizers” and their influences on other somatic treatment in psychiatry. Am J Psychiatry 115: 294-300, 1958
- Anderson BG, Reker D, Volavka J, et al: Prolonged adverse effects from haloperidol in normals. N Eng J Med 305: 643-644, 1981
- Kendler KS: A medical student’s experience with akathisia. Am J Psychiatry 133: 454-455, 1976
- Belmaker RH, Wald D, Haloperidol in normals. Br J Psychiatry 131: 222-223, 1977
- Van Putten T, Mutalipassi LR, Malkin MD: Phenothiazine induced decompensation. Arch Gen Psychiatry 30: 102-105, 1974
- Van Putten T, Mutalpassi LR: Fluphenazine enanthate induced decompensation. Psychosomatics 16:37-40, 1975
- Drake RE, Ehrlich J: Suicide attempts associated with akathisia. Am J Psychiatry 142:499-501, 1985
- Shear K, Frances A, Weiden P: Suicide associated with akathisia and depot fluphenazine treatment. J Clin Psychopharmacol 3: 235-236, 1983
- Weiden P: Akathisia from prochlorperazine (letter) JAMA 253: 635, 1985
- Keckich WA: Violence as a manifestation of akathisia. JAMA 240:2185, 1978
- Schulte JR: Homicide and suicide associated with akathisia and haloperidol. Am J Forensic Psychiatry 6: 3-7, 1985
- Shaw ED, Mann JJ, Weiden PJ, et al: A case of suicidal and homicidal ideation and akathisia in a double-blind neuroleptic crossover study (letter) J Clin Psychopharmacol 6: 196-197, 1986
- Planansky K, Johnston R: The occurance and characteristics of suicidal preoccupation and acts in schizophrenia. Acta Psychatr Scand 47: 473-483, 1971
- Farberow N, Shneidman E, Leonard C: Suicide among schizophrenic hospital patients. In Faberow N, Shneidman E (eds): The Cry for Help, New York, McGraw-Hill, 1965
- Van Putten T, May PRA, marder SR: Akathisia with haloperidol and thiothixene. Arch Gen Psychiatry 41: 1036-1039, 1984
- Klein DR, Gittleman R, Quitkin F, et al: Diagnosis and drug treatment of Psychiatric Disorders: Adults and Children. Baltimore, Williams and Wilkins, 1980
- Donlon PT, Hopkin JT, Tupin JP et al: Haloperidol for acute schizophrenic patients: an evaluation of three oral regimens. Arch Gen Psychiatry 37: 691-695, 1980
- Carter RG: Psychotolosis with haloperidol: Rapid control of the acutely disturbed psychotic patient. Dis Nerv Syst 38: 237-239, 1977
- Anderson WH, Kuehnle JD, Cantanzano DM: Rapid treatment of acute psychoses. Am J Psychiatry 133: 1076-1078, 1976
- Ericksen SE, Hunt SW, Chang S: Haloperidol doses, plasma levels, and clinical response: A double blind study. Psychopharmacol Bull 14: 15-16, 1978
- Rifkin A, Quitkin F, Klein DF: Akinesia: A poorly recognized drug-induced extrapyramidal behavior disorder. Arch Gen Psychiatry 32: 672-674, 1975
- Shackman DR, Van Putten T, May PRA: Micrographia and akinesia. Am J Psychiatry 135: 839-840, 1979
- Van Putten T, May PRA, Wilkens JN: Importance of akinesia: relationship to plasma CPZ and prolactin levels. Am J Psychiatry 137: 1446-1448, 1980
- DeJong RN: The Neurologic Examination, 3rd ed. New York, Harper & Row, 1967, pp 398-400
- Van Putten T: Adverse psychological (or behavioral) responses to antipsychotic drug treatment of schizophrenia. In Rifkin A (ed):: Schizophrenia and Affective Disorders: Biology and Drug Treatment. Boston. John Wright, 1983
- Sacks O: Awakenings. New York, Dutton, 1983
- Van Putten T, Marder SR, Mintz J: The therapeutic index of haloperidol in newly admitted schizophrenic patients. Psychopharmacol Bull (in press)
- Rifkin J, Kane JM: Low dose neuroleptic maintenance treatment of schizophrenia. In Kane JM (ed): Drug Maintenance Strategies in Schizophrenia. Washington, DC, American Psychiatric Press, 1984
- Rifkin A, Quitkin F, Rabiner CJ, et al: Fluphenazine decanoate, fluphenazine hydrochloride given orally, and placebo in remitted schizophrenics: I. Relapse rates after one year. Arch Gen Psychiatry 34: 43-47, 1977
- Rifkin A, Quitkin F, Klein DF: Fluphenazine decanoate, oral fluphenazine and placebo in treatment of remitted schizophrenics: II. Rating scale data. Arch Gen Psychiatry 34: 1215-1219, 1977
- Rifkin A, Quitkin F, Kane J, et al: Are prophylactic antiparkinson drugs necessary? Arch Gen Psychiatry 35: 483-489, 1978
- Steinberg HR, Green R, Durrell JL: Depression occurring during the course of recovery from schizophrenic symptoms. Am J Psychiatry 124: 699-792, 1967
- Wildroe HJ, Depression following acute schizophrenic psychoses. J Hillside Hosp 15: 114-122, 1966
- Kayton L: Good outcomes in young adult schizophrenics. Arch Gen Psychiatry 29: 103-110, 1973
- Sacher EJ, Mason JW, Kolmer HS, et al: Psychoendocrine aspects of acute schizophrenic reactions. Psychosom Med25: 510-537, 1963
- Stern MJ, Pillsbury JA, Sonnenberg SM: Postpsychotic depression in schizophrenics. Compr Psychiatry 13: 519, 1972
- McGlashan TH, carpenter WR Jr: Postpsychotic depression in schizophrenia. Arch Gen Psychiatry 33: 231-239, 1976
- Marsden CD, Parkes JD: Success and problems of long term levodopa therapy in Parkinson’s disease. Lancet 1: 345-349, 1977
- Calesia GG, Wanamaker WM: Psychiatric disturbances in Parkinson’s disease. Dis Nerv Syst 33: 577-583, 1972
- Robins AH: Depression in patients with parkinsonism. Br J Psychiatry 128: 141-145, 1976
- Van Putten T, May PRA: “Akinetic depression” in schizophrenia. Arch Gen Psychiatry 35: 1101-1107, 1978
- Jellnick T, Gardos G, Cole JO: Adverse effects of antiparkinson drug withdrawal. Am J Psychiatry 138: 1567-1571, 1981
- Manos N, Gkiouzepas J, Logothetis J: The need for continuous use of antiparkinsonian medication with chronic schizophrenic patients receiving long-term neuroleptic therapy. Am J Psychiatry 138: 184-188, 1981
- Manos N, Gkiouzepas J, Tzotros T, et al: Gradual withdrawal of antiparkinson medication in chronic schizophrenics: Any better than the abrupt? J Nerv Ment Dis 169: 659-661, 1981
- Van Putten T, May PRA, Marder SR: Response to antipsychotic medication: The doctor’s and the consumer’s view. Am J Psychiatry 141: 16-19, 1984
- Kane JM, Rifkin A, Woerner M: High-dose versus low-dose strategy in the treatment of schizophrenia. Psychopharm Bull 21: 533-537, 1985
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