DIFFERENTIAL TREATMENT OF PSYCHIATRIC DISORDERS
SELECTION OF PSYCHOTROPIC MEDICATION
WITH NOTES ON ALTERNATE MODALITIES
ANIL MITRA PHD, COPYRIGHT ©
1993, REFORMATTED May 2003
Document
status and plan: May 29, 2003
Caution: the information in this document is outdated and is not for use in therapy
I maintain this document out of interest, as a source of ideas – the idea of going directly from psychiatric problem to treatment is interesting and potentially useful, and as the basis of possible future revisions and updates
The document is raw with regard to editing and style
Plans: see Plan
No action for
Journey in Being
OUTLINE
2 Psychotropic Drug Classes
Considered
3 The Common Disorders and Problems
Parkinson’s
Syndrome and Tardive Dyskinesia
Depression
and Related Problems
Anxiety,
sleep and related disorders
Dementias,
confusion, hyperkinesias
4 The Drug Classes: Discussion
Latest
Revision, Copyright and Plan
The purpose of this manual is to briefly display main considerations for selection from an array of medications in treatment of the common psychiatric disorders and problems
For doses, titrations, onset and half-life, drug interactions, contraindications, allergic reactions, and other precautions, and legal and ethical issues, see standard references. For some discussion on allergic reactions -- but not on their treatment -- see the discussion of antipsychotics
May 2003 Caution: the information in this document is outdated and is not for use in therapy
1. Antipsychotics
2. Antineuroleptics
3. Dopaminergic Agents
4. Antidepressants
5. Antimanics
6. Antiaggressives
7. Anxiolytics [Antianxiety] and Hypnotics
8. Stimulants
Note: The one-to-one correspondence between the disorder classes and the drug classes is only approximate in that the correspondence suppresses or fails to display crossover and coadjunct or adjunct therapy
In schizophrenia and schizophreniform and schizoaffective disorders
Delusional [paranoid] disorder
Brief and atypical psychoses; induced psychotic disorder
Associated with substance intoxication, withdrawal
Associated with episodes of mania and psychotic depression
Associated with personality disorders, especially borderline
Personality disorder
In addition to the section on “antineuroleptics”, also see:
Psychotropic Drugs in Medicine, A. Mitra, 1991
Related to Item 2
Adjustment reactions
Suicidal ideation and chronic suicidality
Seasonal affective disorder and cyclothymia
Depressive episodes, chronic depression, dysthymia
Depressive episodes of bipolar disorder and schizoaffective disorder
Childhood depression and related problems
Manic and hypomanic episodes
Maintenance therapy: bipolar disorder
Mania with aggression
Individuals with abnormal electro-encephalograms, especially temporal lobe foci
Aggression secondary to mania, cyclothymia
Aggression due to psychosis [including paranoia]
Due to anxiety, generalized fear, mistrust, hostility
Personality disorders
Chronic aggression in individuals with organic brain diseases
Or injuries
Anxiety and panic: generalized, and in personality disorders;
And secondary psychosis
Sleeplessness [due to anxiety] and sleep disorders
Central nervous system irritation [in withdrawal from
Central nervous system depressants]
Agitated depression
Dementias
Confusion
Narcolepsy
Exogenous obesity [not due to an organic disorder or problem]
Attention deficit [with and without hyperactivity]
[1] Uses, and
[2] Considerations for selection which include: drug subclass; alternative and co-treatment including non-drug therapies; special populations and target symptoms; short- vs. long-acting drugs and preparations; side effects profiles; idiosyncratic response and side effects, allergic reactions; dependence and withdrawal; medications compliance
Uses
Treatment of psychosis and other [dopamine modulated?] neurologic hyperactivity: especially tics and Tourette’s syndrome. Also: Episodic aggression; anxiety/sleeplessness secondary psychosis; in mania/depressive/schizoaffective manifestations for treatment of target symptoms [e.g. florid psychosis], or as co-/adjunct treatment; as anti-emetic [thorazine]; use of dopamine depleting drugs [such as reserpine and tetrabenzene; the common antipsychotics are dopamine blocking] to reduce domapinergic tone in tardive dyskinesia [possible, hypothetical] -- or as alternates, perhaps, to dopamine blockers in cases of akathisia. In mild psychosis associated with borderline personality disorder [as adjunct treatment]
Dimensions: Considerations in
Selection
1. Drug functional class/mechanism:
Dopamine blockers [see “Common Antipsychotics” and “Clozaril and Resperdil”]
Dopamine depletors
[e.g., reserpine, tetrabenzene];
currently of historical interest except in special applications, or when
current antipsychotics are unavailable [“
Dopaminergic agents/agonists [e.g., L-Dopa/amantadine, bromocriptine?] used paradoxically to reduce dopaminergic tone - and so lessens psychosis as delayed side effect
Drugs which enhance antipsychotic activity, e.g., lithium alone, or in combination with other more common, antipsychotics
Drugs which target signs and symptoms of psychosis [e.g., Tegretol in episodic psychosis/behavior secondary to episodic psychosis]
Other drugs for schizophrenia such as propanolol in high doses [hazardous, efficiency not confirmed [1983]] ; and endorphins and other neuropeptides [effectiveness not confirmed [1983]] . Anxiolytics are frequently used for anxiety secondary to schizophrenia/psychosis but there are unconfirmed claims that they are also effective as co-treatment of schizophrenia/psychosis
2. Short- vs. long-acting [decanoate, enanthate … ]. Factors: acute vs. chronic, inpatient vs. outpatient, medication compliance
Currently, long-acting forms of Haldol and prolixin are available
3. Idiosyncratic. Although there may be no difference in the effectiveness of dopamine blockers on schizophrenia/psychosis, there are idiosyncratic differences from patient to patient. This is determined by individual history and secondarily by family history of treatment
4. Effectiveness depends on class of signs and symptoms regarding dopamine blockers. Their effectiveness on signs and symptoms is as follows:
Positive signs and symptoms [hallucinations, delusions] - most effective
Negative signs and symptoms [apathy, low drive, poverty of speech] - less effective
Disturbance of general functioning - least effective
5. Chemical class within blockers [see “Common Antipsychotics” and “Clozaril and Resperdil”]. Knowledge of these classes is important in relation to idiosyncratic efficacy and side effects
6. Side effects profile:
A. Extrapyramidal syndromes [EPS]. The high potency blockers are generally more associated with acute effects of dystonia, akathisia … while the low potency blockers are more associated with long-term effects: tardive dyskinesia
B. Clozaril stands apart with regard to side effects profile. EPS are minimal but it is commonly [initially] associated with tachycardia and low-grade fever. It is occasionally associated with [fatal] agranulocytosis and Clozaril therapy requires careful consideration and blood-count monitoring [weekly: 1994]. Clozaril may be indicated, and is frequently successful in individuals whose condition is refractory to the other antipsychotics
C. Allergic reactions
The following considerations apply to all drug classes:
Allergic reactions may be mild [itching], moderate [rash, nausea, fever] or severe [anaphylaxis, death]. Allergic response may be idiosyncratic: upon the first use, soon after initiation of a medication regimen, or after extended therapy; and there may or may not be a warning: the lesser reactions may or may not precede the severer reactions. When the milder reactions are suspected, it may be prudent to suspend or to initiate alternate therapy; in all cases an alert should be maintained. Allergy to a specific drug or drug class may disappear -- this, too, is [partially] idiosyncratic
Allergic reactions are not drug class or mechanism specific side effects. Patients may confuse drug-specific side effects with allergies. Some patients may also report allergies due to psychiatric conditions: paranoia; or patients may be untruthful -- out of resentment, attention seeking, not wanting treatment, or because the side effects are unpleasant
An allergic reaction is an immune system specific response and, because of the life-threatening possibilities, allergies should be positively and accurately identified
Keys to diagnosis are [i] the special problems of the confused, paranoid, delusional, personality disordered, or dishonest patient [error on the side of safety is usually preferred]; and eliciting accurate information from these patients; [ii] differentiation between side effect and allergies; [iii] questioning [oral history]; [iv] observation and monitoring; [v] individual history -- of allergic reactions to specific medications or medication classes; [vi] family history regarding the factors of the individual history
There may be cases where mild reactions or the risk of severe reactions are tolerated because of the need for therapy. Such cases should be under supervision and monitoring for onset of reactions; facilities adequate to treatment of anaphylactic shock should be available
7. Other therapies:
A. Electroconvulsive therapy [ECT]: Both ECT and pharmacotherapy are regarded as effective in treatment of schizophrenia. ECT is generally of shorter duration. Pharmacotherapy is generally more effective but ECT is more effective in catatonia and may also be indicated when three or more months of pharmacotherapy produce no effect
B. Hemodialysis - Initially generated excitement but initial hopes were not confirmed
C. Psychotherapy and related therapies. Structured, directed and mutual support groups aimed at self-esteem and independent function. Case management
Generally, pharmacotherapy is regarded as the most effective treatment of schizophrenia. However, the issue is complex and the following may be noted:
Some psychoanalysts believe that psychodynamic-psychoanalytic therapy is ineffective when a transference relationship cannot be formed … Of the major mental illnesses, schizophrenia is probably least amenable to pscyhotherapeutic treatment
Related therapies such as family therapy [for support and group symptomatology - schizophrenics most commonly come from families which display schizophrenic personality styles without psychosis … note this is a more effective predictor or epidemiologic factor than socio-economic class] and activity therapy including grooming, socialization, art [for acceptance, self-esteem and evocation of special skills] may play at least an ongoing and supportive role
Antipsychotic medication alone is insufficient for treatment of [chronic?] schizophrenia. In combination with pharmacotherapy, insight-oriented therapy and reality-adaptive-supportive therapy [RAS] are equally effective, perhaps, but RAS is less personnel intensive
The issue of psychotherapy vs. drug therapy remains complex. Although drug therapy may, in fact, be numerically “more efficient”, such superiority ignores [or is too coarse for] the following:
Criterion of effectiveness. In many applications we may ask - is pharmacotherapy “therapy” or control? Also, is therapy maintenance or health?
Mental and personality factors of the individual therapist
Acute vs. chronic forms and styles of schizophrenia [over and beyond the hebephrenic and disorganized, paranoid and catatonic subclassifications]
The mental-personality characteristics of the therapist … These include not only intellect, but perception, sensitivity, concentration, will, “charisma”, experience and, no doubt, others
The issue of whether [and when] a “schizophrenic break” is an illness or the beginning of a healing process, and whether, in the latter case, pharmacotherapy, or any therapy which [merely] eliminates the signs and symptoms, is abortive … No doubt, this includes elements of choice [to under-go the process or to abort it] … It is also a consideration whether the process is one of healing or whether it may also be one of growth
General socio-economic and political issues
The issue of healing as “cure” or “catalyst”
Generally, note that the human mental-personality-socialization system is probably the most fine-grained, complex system known [even including the neuro-anatomical, physiological aspects] and it is not unreasonable to expect that “treatment” would be equally fine-grained -- at least in certain cases … Of all the treatment modes external to the individual, another individual is the only possible current agent which can match the “disturbance” for its [sometimes] complexity -- or which is likely to engage the individual’s own healing ability
The issue of healing as “cure” or “catalyst”
Common Antipsychotics
Phenothiazines
Aliphatic - Thorazine
Piperidine - Mellaril, Serentil
Piperazine - Trilafon, Stelazine, Prolixin
Thioxanthenes
Navane
Butyrophenone
Haldol
Dibenzoxazepine
Loxitane
Dihydroindoline
Moban
Dephenylbutylpiperidine
Orap
Clozaril and Resperdil
Resperdil is a newer antipsychotic [1994]. There are claims that its side-effects profile is similar to that of Clozaril and that it is effective in treatment of the negative symptoms of schizophrenia. Further clinical experience and research are necessary for evaluation of the potential of the drug Resperdil
Uses
Treat side effects of neuroleptics - primarily the side effects of the common antipsychotics; but also other psychotropic, especially antidepressants and among these especially amoxapine [chemically similar to loxapine]
Dimensions
1. Extra-pyramidal syndrome - The specific side effect being considered: acute dystonia, akathisia, akinesia, tardive dyskinesia, … neuroleptic malignant syndrome
2. Class [functional, chemical] of the antineuroleptic: affects the choice of target extra-pyramidal syndrome. Anticholinergics, dopamine agonists, beta blockers, muscle relaxants, benzodialepines, antidopanimergic drugs
3. Side effects of the antineuroleptic itself; an example being the dopamine agonist amantadine [Symmetrel] which has minimal anticholinergic effect
4. Treatment of anticholinergic poisoning
Signs and Sypmtoms - by anticholinesterase
Cause - by physostigmine salicylate and pyridostigmine bromide
[These are cholinergics and result in cholinergic stimulation which may be treatment by atropine.]
Uses
Treatment of neuromuscular hypoactivity and Parkinson’s syndrome; acute dystonia secondary to use of antipsychotics; “paradoxical” treatment of tardive dyskinesia - e.g., L-dopa to desensitize the post-synaptic dopamine receptor [hypothetical]
Uses
Treatment of depression; of suicidal ideation and/or a history of suicide attempt. Treatment of depression and suicidality by antidepressants requires monitoring to prevent potentiating action as depression lifts. Co-treatment involves therapy. Some “specialized” uses: seasonal affective disorder [enhanced by daily exposure to bright light]; monoamineoxidase inhibitors are effective in depressive episodes of bipolar disorder; Prozac appears to be effective in treatment of borderline personality disorder; desipramine, Anafranil and Prozac for obsessive-compulsive disorder; imipramine is the most widely researched drug used in treatment of children and is used to treat a range of childhood disorders including:
bipolar disorder; schizoaffective disorder and psychotic depression [imipramine is the heterocyclic antidepressant of choice since it tends less than the other hetero-cyclic antidepressants to potentiate psychosis]; anxiety that is secondary to depression; school refusal and other behavioral problems; enuresis [Elavil is an alternate to imipramine]; night terrors - sleep-terror disorder - in combination with valium; “borderline” children. Elavil and thorazine are sometimes used in combination for treatment of anorexia nervosa. Generally drug treatment is in combination with other modes
Dimensions
1. Drug class: monamine oxidase inhibitors; hetero-cyclic antidepressants and trazodone; Prozac [flouxetine] and fluvoxamine; and Wellbutrin [bupropion]
Hetero-cyclic antidepressants are the most commonly used [1991] and have anticholinergic and cardiac effects [depresses cardiac function]. Trazodone [Desyrel] is similar in structure to hetero-cyclic antidepressants -- but has little anticholinergic and cardiac effect, has a sedative effect, and can cause dangerous priapism in males
2003 NOTE: In addition to Prozac, there are a number of newer, selective serotonin re-uptake inhibitors: Zoloft [sertraline,] Paxil [Paroxetine,] Celexa, and Lexapro; additionally Luvox is an selective serotonin re-uptake inhibitor as is Effexor at low doses
Monamine oxidase inhibitors are indicated [1] when hetero-cyclic antidepressants, selective serotonin re-uptake inhibitors, and electro-convulsive therapy are contraindicated or ineffective, [2] in depressive episodes of bipolar disorder
The selective serotonin re-uptake inhibitors and fluvoxamine have low anticholinergic, cardiac and sedative effects compared to hetero-cyclic antidepressants … It is claimed that Wellbutrin has similar performance and lack of side effects; however this is not borne out by immediate clinical experience. It is speculated that Wellbutrin is not an selective serotonin re-uptake inhibitor; it may effectively treat the “negative symptoms” of schizophrenia
1994 NOTE: A relatively new antidepressant Effexor is reported to be a potent inhibitor of serotonin and norepinephrine re-uptake -- and a weak inhibitor of dopamine re-uptake; effexor is an “activating” antidepressant
2. Other treatment: Daily exposure to bright light affects depression especially seasonal affective disorder; partial sleep deprivation has some value in treating depression - This is elongated by use of lithium; electro-convulsive therapy is an effective treatment of depression and is indicated when hetero-cyclic antidepressants [and the more recent drugs, the selective serotonin re-uptake inhibitors and Wellbutrin] are ineffective and/or for deep depression
3. Idiosyncratic differences in response by different patients. Determined first by individual history and then by family history
4. Side effects profile and special symptoms:
Hetero-cyclic antidepressants. The earlier hetero-cyclic antidepressants [especially Elavil] are most harsh with regard to side effects. Amoxapine being similar in structure to antipsychotics tends more than others to produce extra-pyramidal syndrome. The derivative compounds are more potent, and produce milder side effects. Trazodone is included here because its structure is similar to that of hetero-cyclic antidepressants and has minimal anticholinergic and cardiac effects. Anafranil is also used for phobic anxiety and severe obsessive-compulsive disorder. Other special applications are noted under “uses”
Fluoxetine [Prozac] and fluvoxamine [Luvox] are identical to hetero-cyclic antidepressants for treatment of depression. Fluvoxamine is claimed to offer a treatment for obsessive-compulsive disorder as effective as that of clomipramine [Anafranil] but is better tolerated. Compared to fluoxetine, fluvoxamine has a much shorter half-life of elimination and has less potential for agitation, insomnia and drug interactions
Uses
In mania [manic episodes of bipolar disorder]; in maintenance -prophylactically, against manic episodes; in aggression control. In all cases adjunct [drug/psycho-] therapy is recommended
Dimensions
1. Drug/Class: Lithium [carbonate/citrate]; anticonvulsants [Tegretol - especially in aggression control, Klonopin, Depakene, valproic acid; also Depakote or valproate sodium]; calcium channel blockers [Verapamil]; alpha-adrenergic agonist [clonidine]; beta-adrenergic receptor blocker [Inderal]
2. Other/co-treatments: Antipsychotics are often used for symptom and aggression control: they act rapidly; lithium is started with antipsychotics -- and then maybe the antipsychotic withdrawn as the psychosis and/or aggressive behavior respond to the treatment
3. Symptom profile: Tegretol is used separately or together with lithium in cases where lithium does not control aggression. Anti psychotics/beta blockers are used for delusions secondary to mania
4. Side effects profile: Tegretol is used when lithium is not tolerated or produces paradoxical effects [1994]
Dimensions
1. Drug/Class:
Anticonvulsants: Tegretol -- use with normal and abnormal electro-encephalograms -- especially temporal lobe foci. Also: Dilantin, primidone
Lithium: aggression/irritability, secondary mania/cyclothymia [supplement with or replace by Tegretol if lithium insufficient or contraindicated]
Antipsychotics: episodic aggression of aggression secondary to psychosis
Sedative-hypnotics: Episode control [problems of paradoxical rage and hostility]: anxiety, and personality disorders [treatment or co-treatment]
Beta blockers: chronic and recurrent aggression in patients with organic brain diseases or injuries … and/or where aggression is not directly related to psychosis and psychotic ideation
2. Etiology:
Mania: Lithium, Tegretol [ … ]
Brain disorders: Inderal, Tegretol [other beta blockers]
Psychosis: antipsychotics
Chronic and recurrent aggression and irritation not secondary to psychosis: Inderal, other beta-blockers
Acute management of violence and agitation, not secondary to psychosis: sedative or hypnotic-Anxiolytics including sedative effect of antipsychotics
3. Other treatments:
Psychotherapy [during post episode phase]
Direction, support [pre-episode]
Physical containment and restraint
Long-term therapy
Electro-convulsive therapy [perhaps]
4. Population: Lithium carbonate [LiCO3] and citrate is used to control aggression in the following specific non-bipolar populations:
Developmentally delayed
Behavioral disorders of children/adolescents
Head injury, organic brain syndrome
First degree psychiatric disorders [other than bipolar disorder]
Epilepsy
Prison populations
Uses
Treatment anxiety and panic: Primary to and secondary to other disorders and circumstances including a predisposition to circumstantially induced anxiety; treatment of consequences of anxiety: sleeplessness, irritability and aggression, lowered function and possibly psychosomatic manifestations; primary and secondary sleep disorders especially sleeplessness and poor sleep [insomnias]; withdrawal from central nervous system depressants; anaesthetic applications
Anxiolytics are also used for control of anxiety in episodic manifestations of borderline personality; co-treatment with a low potency antipsychotic [frequently Mellaril] is used to control psychotic features such as delusions, paranoia, racing thoughts
Dimensions
1. Sleep-anxiety: In case of benzodiazepines, the specific drug is chosen by experience and history. Shorter acting drugs are less addictive
2. Drug Class: Benzodiazepines are current anxiolytics-hypnotics of choice; antihistamines Atarax [Vistaril] and Benadryl are also frequently used; other classes: barbiturates, barbiturate-like compounds and other non-benzodiazepine, nonbarbiturate compounds are not current drugs of choice - chloral hydrate is possibly a carcinogen but continues to find occasional use in control of refractory insomnia with aggression; non-prescription compounds include diphenhydramine [benadryl], methpyrilene and pyrilamine, salicylamide, scopolamine aminoxide and scopolamine hydrobromide [used in Compoz, Nytol, scopolamine, Sleep-eze etc.]
3. Length of action:
Shorter acting substances: reach steady state sooner, are more suitable for single [and as needed] dose, produce less morning drowsiness, are less severely addictive
Longer-acting substances: Are suitable for maintenance and multiple dose applications, produce less severe withdrawal; are used in withdrawal from central nervous system depressants
Some Benzodiazepenes:
Anxiolytics: Xanax [I],* Librium [L], Tranxene [L], Clonopin [ L], Valium [L], Paxipam [I], Ativan [S]
Hypnotics: Serax [S], Centrax [L], Dalmane [L], Restoril [S], Halcion [VS], Dormalin [L], Nitrazepam
Food and Drug Administration designations: L = long-acting, I = intermediate, S = short; VS = very short
Uses
1. In depression - especially initial treatment of depression and paradoxical treatment of agitated depression
2. Treatment of dementias [especially in geriatrics],
3. Treatment of confusion; production of alertness and wakefulness; as an antihypnotic; treatment of narcolepsy
4. Treatment of exogenous obesity
5. Treatment of hyperkinetic syndrome in children. General use to treat hyperactivity is clearly questionable; “legitimate” treatment of attention deficit hyperactivity disorder and of attention deficit [without hyperactivity]; [the concept is analogous to use in treatment of depression … the effect is “paradoxical”: it is assumed that the hyperactivity is secondary to lack of concentration with a causal sequence similar to: attention deficit-> confusion-> agitation-> hyperactivity.]
Dimensions
1. Other treatment: Therapy for exogenous depression, attention deficit etc.; co-treatment with other drugs: antidepressants …
2. Use:
3. Dependence:
4. Order of preference: hyperactivity secondary to attention deficit: Ritalin; if ineffective try d-amphetamine [numerous contraindications]; then Magnesium premoline; then Thorazine may reduce hyperactivity without increasing attention
ANIL MITRA PHD, COPYRIGHT ©
1994, REFORMATTED May 2003
It must be emphasized again that the information here, though useful, is
outdated and I recommend against its use in therapy
I maintain this document out of interest, as a source
of ideas – the idea of going directly from psychiatric problem to treatment is
interesting and potentially useful, and as the basis of possible future
revisions and updates
If the occasion arises I will rewrite this document:
Incorporating newer drugs
Information to online sources; other references
Improved considerations for selection especially neurotransmitter
selective information, patient profiles, target populations and problems,
multiple drug therapy – within and across psychotropic drug classes, drug
interactions including medical problems, approaches to minimizing polypharmacy, and co-therapies [see Psychotherapies]
…and improved categories of sub-head under the disorders and drug
classes
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