PSY 3007 - Abnormal Psychology and Psychiatry - complete lecture notes

Abnormal Psychology and Psychiatry – Lecture 1

Core texts:
- Psychiatric Drugs Explained – David Healy
- Psychiatry and the Human Condition – etc www.hedweb.com/bgcharlton
- Texts of psychiatry and abnormal psychology
- www.mentalhealth.com
- Google and PubMed
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Emotion
Lecture is a general model of an important psychological mechanism of psychiatric symptoms - and a powerful way of conceptualizing drug actions

My website
– Psych and the HC esp - Awareness, consciousness and language;
– Idea of Antonio Damasio

Problem of psychiatry – understanding how drugs interact with behavior. How can eating chemicals make you feel better, function better?

Basic model of cognitive psychology
Brain as information processing device - input/ process/ output.
Brain states many represent perceptions of external environment - eg vision, hearing, touch, smell, taste - so that (for eg.) patterns of nerve activation represent particular aspects of the visual scene. - outside the body.
But emotions represent body states. i.e. Emotions are patterns of nerve activation in the brain that represent the internal environment.
Emotions probably correspond to characteristic body states as they are sensed by the brain.
The brain senses the body by nervous and chemical means - the nerves of autonomic nervous system (the sympathetic and parasympathetic systems), and chemical information is obtained by specialized parts of the brain monitoring the concentration of hormones.
Brain is monitoring the body, continually updated picture of what is going on in the body, and can initiate appropriate behaviors in response to these body states.

What are the emotions?
The number and type of emotions corresponding to body states is not yet known. A good example to understand the cognitive nature of emotions.
One idea, by Ekman, is that emotions correspond to facial expressions - fear, anger, surprise, disgust, happiness/ joy, sadness/ distress. Discuss
But one of the emotions is almost certainly fear. This is relevant to the anxiety based forms of psychiatric illness - Generalized anxiety, phobias, panic disorder and obsessive-compulsive disorder.
Fear is a response mediated by the sympathetic nervous system, it prepares the body for action (fight or flight) - increased heartbeat, faster breathing, increased alertness, blood diverted to the muscles etc.
Fear can be conceptualized as a primary and a secondary emotion.

Primary emotion – Fear could occur in response to a perception, for example the primary emotion of fear in response to seeing a tiger.
Secondary emotion – Fear could occur in response to cognition, in other words thinking about a tiger - in response to modeling in one’s own mind the situation of being attacked by a tiger.
Secondary emotions probably only occur in humans and other animals capable of conscious thought - such as chimpanzees.
· The emotional state/ body state is the same for primary and secondary emotions - however primary emotions are triggered by perceptions while secondary emotions are triggered by cognitive modeling. This explains how emotions can occur even in the absence of stimulus.

Importance of emotions to psychiatry and abnormal psychology
1. Emotions link social behavior and emotions - we use emotions to judge social situations. Emotion and social symptoms are probably the commonest in psychiatric illnesses in general.
2. Emotions provide a model for psychiatric drug actions
Anything which changes the emotional body state, or the brains perception of body state, may affect emotions.
If a drug blocks the physical changes of anxiety, then body state change will be monitored by the brain and reduce the perception of anxiety. Eg diazepam/ Valium relaxes muscles, propranolol slows the heartbeat.

PSY3007-2 – BZs - Benzodiazepines and
SSRIs - Selective serotonin-reuptake inhibitors
· http://www.healyprozac.com/
· Sobo, S. Psychotherapy perspectives in medication management. http://www.psychiatrictimes.com/p990423.html
· My paper and book ‘… and the human condition’, ‘palliative’ also S-DTM paper.

As benzodiazepines were for the 70s and 80s, so the SSRIs are for the 90s and 00s – main class of drugs used to treat anxiety symptoms (and mild depression).
Among the most profitable medications of their era.
Similar trajectory from hyped wonder drug to villain.

Benzodiazepine Anxiolytics
Examples - diazepam (Valium), chlordiazepoxide (Librium) - long-acting; alprazolam (Xanax) - short-acting, clobazam (Frisium) – not-v-sedating.
Benzodiazepines introduced in 1960s as a substitute for the barbiturates: less sedative , less hangover, less addictive, safer in overdosage.

Mode of action
Act to modulate GABA neurotransmitter - major NT responsible for inhibition of neurons.
BENZ may be synthetic equivalent of natural brain chemicals called beta-carbolines.

Clinical Effects -
1. Subjective - soothing, relaxing like alcohol.
2. Anti-anxiety - especially when anxiety due to muscle tension
3. Muscle relaxation - diazepam is one of the best muscle relaxant drugs, used for spasm and spasticity.
4. Sedative - usually produces sleep in high enough doses - but variable between individuals. Some are not sedative - eg clobazam (Frisium).
5. Anti-convulsant - used in treatment of acute epilepsy and in withdrawal of alcohol or heroin
6. Control of violent behavior and acute psychosis - eg acute schizophrenia or mania. Usually lorazepam.

SIDE EFFECTS -
Rebound anxiety and insomnia. Quality of sleep is inferior to natural sleep.
Release of violent or antisocial behavior - like alcohol.
Dependence - probably a susceptible minority => < month.
Abuse - especially IV especially temazepam.
Now typically used for short periods, perhaps under-used given comparative safety and pleasantness.

SSRIs
Prozac - fluoxetine; Cipramil - citalopram; Seroxat/ Paxil – paroxetine, Lustral/ Zolofy – sertraline, Faverin/ Luvox – fluvoxamine, .
The only important group of psychy drugs to be discovered in ‘recent’ years (1970s).

Clinical use
Different from benzos - different kind of anxiolysis.
Used in outpatient depression, panic, social phobia and other generalized phobias, OCD, GAD.
Many people have had lives transformed for the better. Others unaffected, others worse.
Misunderstood to be ‘happy pills’ like barbiturates or cocaine - but do not make people euphoric (like BZs can) - almost the opposite.
More like a mild kind of emotional blunting – like a mild neuroleptic – as would be expected from their chemistry. May make people more ‘stable’, emotionally more robust/ less strongly emotional.
Therefore may make people more sociable, less shy, less prone to downward mood swings - but some people may also or instead feel that mood upswings are impaired.
Or, emotion-blunting, reducing extremes of emotion, hardening of personality – less caring and empathic.
Make some people more cool and sociable and confident; make other people cold, detached and indifferent. May cause break up of relationships – this may be a good or bad thing.
‘Serenic’ agent in some people - demotivating in other people

Addiction or dependence
Not classic ‘addictive’ euphoriant drug like heroin or cocaine.
But SSRIs may produce also dependence (eg paroxetine) – hard to stop taking without side effects.
Dependence may be hard to differentiate from original problem – need trials in normal volunteers. But dependence to SSRIs was noted in healthy volunteers during drug development.
Probably all psychotropic drugs have potential to induce dependence since they are alien substances which the brain and body need to ‘adapt’ to – when withdrawn the system needs to restore equilibrium. Withdrawal symptoms are mainly depression and anxiety.
Sometimes get ‘poop-out’ when drug seems to stop working – may respond to increased dose.

Unwanted side effects
Nausea and vomiting - usually wears off.
Akathisia – agitation and restlessness - rare but serious. Stop drug.
Rarely (< 1:1000) people feel acute mental turmoil, acutely suicidal with bizarre violent fantasies (eg about violent death) – may lead to suicide. Not used in children for this reason

Antidepressant, or anxiolytic
When launched, the benzodiazepines had become very unfashionable, vilified for their addictive and abuse potential. This worry spread to any anxiolytics.
The tendency was to diagnose what would have been anxiety as either depression or specific anxiety disorders such as panic, OCD, and phobias.
Move from early 90s to reduce suicide rates, main ideas was to treat undetected depression, mainly with antidepressants which had been shown to reduce suicide in tricyclic studies of rare moderate to severe hospital depression – the assumption was that this would transfer to common, mild, primary health care ‘depression’ treated with SSRIs.
In fact early, unpublished studies done by pharmaceutical companies tended to show increased rate of suicide on SSRIs – as is now known. Seems confirmed by retrospective analysis – severalfold increase in suicide on SSRIs. But tho’ flagged up more than 10 years ago, still no trials…

Issues raised by SSRIs
· Very widely prescribed but very poorly understood – eg. Why no suicide trial? Sheds light on interaction between marketing and science.
· Used by ‘normal’ people who experience psychiatric symptoms but who do not have a formal diagnosis. Response is very individual - may feel better, worse, or no effect.
· Raise question of ‘cosmetic’ or ‘palliative’ psychopharmacology - availability and mode of prescribing - eg analogies with oral contraceptive pill, or with analgesics.
· Self-treatment eg: Diphenhydramine, Chlorpheniramine, St John’s Wort.
***

PSY 3007-3 Generalized anxiety, Panic & Phobic disorders

REFERENCES
DSM-IV and ICD-10 - http://www.mentalhealth.com

Anxiety is a kind of fear, unpleasant increase in arousal - probably a universal experience - although magnitude is very variable.
A universal biological category, cross-cultural, once of the basic emotions an adaptive response – improves reproduction/ survival: increases arousal.

Hypophobia
? Maladaptive if LACK of anxiety - increase accidents etc. “Hypophobia”, Isaac Marks. Absence of fear of heights in children associated with more serious falls – and instead of developing a fear of heights they are still less afraid of heights as adults.

Evolved fears
Many fears are non-associative/ evolved eg. fear of the dark, of being alone, of strangers – we do not learn these fears – on the contrary we learn to overcome them.
Anxiety disorders may be more a failure to learn to overcome fears, rather than learning of fears.
RG Menzies and JC Clarke evolved fears:
1. danger to species
2. avoidance increases reproductive success
3. under genetic influence

Psychological symptoms - mental anxiety: dread, worry, irritability/ sensitivity, restless, poor concentration. Maybe intrusive and distressing thoughts or impulses
Physical symptoms and signs - Tension - from suppression of action: essentially muscular tension.GI, heart, RS, GU, Neural - ie. Sympathetic nervous system over-activity including adrenal gland hypersecretion.

GENERALIZED ANXIETY DISORDER (GAD)
Used to be termed just Anxiety
Chronic unrealistic or excessive anxiety (about 2 or more themes) - for most of the time and for several months at least. NOT phobic, obsessive, hypochondriac or panic.
The person may have good reason to be anxious, but the anxiety has become maladaptive, prevents them doing anything constructive. Or else the causal problems may be intractable.
Epidemiology - not known ?maybe 5%-ish. Depends on definition - no clear division between those with and those without. Many people self-medicated.

Treatment:
1. Relaxation - especially self-hypnosis, learned muscle relaxation; and Supportive discussion, explanation, advice
2. Cognitive-behavioral - difficult, no specific entry point.
3. Drugs :
· Alcohol (self-medication) - far more dangerous than most of the drugs. Impairs cognitive function and many aspects of performance, causes violence and accidents.
· Benzodiazepines – muscle relaxation, tranquillizing/ calming
· SSRIs - emotional buffering
· Beta-blockers - eg propranolol - peripheral effects, reduce feedback to brain. Unpleasant in high doses.


PANIC DISORDER
Disabling anxiety

Rapid build-up of anxiety
Physical symptoms prominent - palpitations, shaking, nausea
Fear of a catastrophic outcome - heart attack, fit, collapse
?Unpredictable precipitant
Hyperventilation common - feel breathless

Epidemiology- ?c 1.5% prevalence in one year men; 3% in women.

Evolutionary Significance
? Triggering of suffocation-avoidance response
?? Separation anxiety - project with Sarah Matthews - not to avoid danger, but signal for assistance (from family group) like a child.


Treatment
Re-breathing of CO2 (although some claim this is ‘occupational therapy’)
Cognitive therapy - implications of attack (eg. MI, epilepsy) - induce symptoms
Tricyclic antidepressants - usually imipramine (advocated by discoverer of panic disorder - Donald Klein).
SSRIs, Benzodiazepines - eg. alprazolam spec marketed. Promoted along with panic disorder, and to distance from other benz - got licensed for this.

PHOBIC ANXIETY
Anxiety in relation to particular circumstances
Avoids situation
Anticipatory anxiety

Specific/ Simple phobia
eg: spiders, snakes, heights, dentists, flying.
General phobia
· Agoraphobia
· Social phobia

Simple
Treatment - Behavioral Therapy. Utilize habituation by seeking out exposure to stressor, block avoidance activities.
Eg. exposure therapy, graded exposure. Sometimes antidepressants, esp SSRI
Agoraphobia - long lasting may have poor prognosis - nip in bud.

Evolutionary significance
Nature of phobia - fear is best if switched-on at need. Costs and benefits of XS fear. (eg. timid guppies survive in double the numbers as bold ones). Avoidance may be best policy.
But fear that is on average adaptive in ancestral environment may be maladaptive under modern conditions - often understandable in this light. Eg fear of snakes or spiders and social phobia would have been legit under ancestral condits. .
Social Phobia. DSM IV
1. Fear of social or performance situations in which the person is exposed to unfamiliar people/ scrutiny by others. Fears that will act in a way (or show anxiety symptoms) humiliating or embarrassing.
2. May take form of a situationally-bound Panic Attack.
3. The feared situations are avoided or intense anxiety.
4. Avoidance or distress interferes significantly with normal life.
5. Duration is at least 6 months.


Treatment
Probably CBT is treatment of choice
The cognitive component - For example, a person with social phobia might be helped to overcome the belief that others are continually watching and harshly judging him.
The behavioural component of CBT seeks to help people become less anxious in the situations that frighten them. Key element is exposure, in which people confront the things they fear.
The exposure process generally involves three stages. First, a person is introduced to the feared situation. The second step is to increase the risk for disapproval in that situation so a person can build confidence that she can handle rejection or criticism. The third step involves teaching a person techniques for coping with disapproval.
In this stage, one is asked to imagine his worst fear and is encouraged to develop constructive responses to his fear and perceived disapproval.
These stages are often accompanied by anxiety management training -- for example, teaching people techniques such as deep breathing to control their anxiety.
But SSRIs probably commonest (quicker, cheaper) – especially associated with Paroxetine (Paxil/ Seroxat) who got a licence for SP a few years ago and marketed the disease.


PSY 3007 – 4 OCD - Obsessive Compulsive Disorder and PTSD Post-Traumatic Stress Disorder

OCD
Obsessions – cognitive
Subjective unwanted/ distressing/ inappropriate thoughts (alien but recognized as personal)

Compulsions – behavioural
Objective actions - quasi-rituals, performed unwillingly, with anxiety and inner struggles, to get relief from…
Indecisive, cannot take action
Mood state - usually anxious, may be depressed

Obsessions -
1. Thoughts - words, phrases, rhymes
2. Images - eg violent, disgusting
3. Impulses - eg violent, shameful
A fear that they will act on these obsessions

Compulsions - rituals, maybe specific number of repetitions

Epidemiology - c2% population prevalence and 2% chance of having it in lifetime – (unusually) same prevalence in men and women. Same sex incidence implies that it is not a classic ‘anxiety disorder’. Some degree of intrusive thoughts almost universal.

Aetiology (cause)
Unknown, small (5% parents) tendency to run in families
?genetic; some abnormality of serotonergic system of brain.
Prognosis (outlook) - 2/3 improve in a year - but may persist for decades.

Treatments
1. Explanation, reassurance, support…
2. Cognitive-Behavior therapy
Can treat objective compulsions effectively eg rituals by Exposure and response/ritual prevention – eg a patient who fears germy things and washes hands must be exposed to germy things and not wash hands until anxiety subsides. Often relate to invisible (technological) things like germs, gas, minute quantities of poison etc. Learn that feared outcome does not happen.
Less effective for obsessive thoughts. Cognitive therapy (CT), which may be added to E/RP, addresses such things as faulty estimation of danger or the exaggerated sense of personal responsibility often seen in OCD patients.
Thought experiment – patients encouraged to try and do (with mind) the thing they fear (eg harm someone).
Thought stopping – distraction. Think about the intrusive thought in relaxed environment then therapist unexpectedly shouts STOP! – moves to thinking about pre-prepared image. Aim to espablish a connection.
3. Drugs - SSRIs (? Because work serotonin neurotransmitter systems) - clomipramine (tricyclic) also serotonergic. MAOI – eg. phenelzine.

PTSD – Post-traumatic Stress Disorder
Introduced in 1980 DSM III, following return of veterans from Vietnam War. Main similarity is with ‘combat fatigue/ shell shock’.

Diagnosis
1. Delayed/ protracted response to severely stressful or traumatic event (war, disaster, torture, violence, RTA most frequent) – latency of weeks/ months < 6 months
2. Intrusive memories/ flashbacks - Symptoms of re-living (feel real, maybe partial – or images like a movie, maybe when recovering) nightmares
3. Distress at reminding cues
4. Avoidance of possible cues
5. High arousal, hyper-vigilance, low startle threshold, insomnia +/- background of numbness/ emotional blunting

Now NIMH estimate of 4% of adult population at any one time with PTSD (but can occur in all ages).
Twice as many women as men (in line with most anxiety disorders – women have a lower threshold for fear in relation to physical violence/ harm, related to their evolved concern with physical self-preservation).
Higher than population rates of PTSD-like syndromes in combat troops – maybe two or more fold greater – but depends on casualty rate, nature of fighting, duration of fighting, training, leadership
But always a certain percentage of psychological casualties – range between 2 percent and 50 percent.

Conceptualizing cause
Evolutionary perspective Secondary Emotion - Memory for events is laid down with memory of emotions experienced at the time (state-related).
When events are recalled, emotion is re-experienced, re-enacted
When body is in the same emotional state, event-recall may be triggered.

Treatment
Similar to other kinds of specific anxiety -SSRIs,
Mood stabilizers (eg sodium valproate – anti-epileptic) anti-irritability/ anger

Psychotherapy
1. Relaxation training
2. Cognitive therapy: helping to modify unrealistic assumptions, beliefs, and automatic thoughts that lead to disturbing emotions and impaired functioning. For example, trauma victims often have unrealistic guilt related to the trauma
3. Exposure therapy: learning to confront specific situations, people, objects, memories, or emotions associated with stressor
· Imaginal exposure: the repeated emotional recounting of the traumatic memories until they no longer evoke high levels of distress.
· In vivo exposure: repeated confrontation with situations that are now safe, but which the person avoids because they have become associated with the trauma and trigger strong fear (e.g., driving a car again after being involved in an accident) Person learns that the feared situation is no longer dangerous

Evolutionary similarity of OCD and PTSD – learning to avoid harmful situations, and remembering of emotions as well as information. Recall of emotions (secondary emotions) causes emotions to be replayed in the body, re-live the body state of the event remembered. Therefore - Prob OCD and PTSD are extreme and maladaptive versions of normal psychological mechanisms.

PSY 3007 - Lecture 5 Depression, SAD

Listening to Prozac by Peter Kramer
My book and papers on website - www.hedweb.com/bgcharlton esp Malaise Theory of depression

Kraepelin - c 100 years ago divided the functional psychoses between Schizophrenia and the ‘affective’ psychoses, or mood disorders.
Idea that mood is the core abnormality - depression = ‘low’ mood.
Core status of mood is not sustainable. What is mood? - hard to define precisely. Something like average emotional state. The same mood can be produced by many causes - like pain.

Depression
Syndrome – DSM IV Major Depressive Disorder (or Depressive Illness or Melancholia)
Diagnostic Criteria
At least one of the following three abnormal moods which significantly interfered with the person's life:
1. Abnormal depressed mood most of the day, nearly every day, for at least 2 weeks.
2. Abnormal loss of all interest and pleasure most of the day, nearly every day, for at least 2 weeks.
3. If 18 or younger, abnormal irritable mood most of the day, nearly every day, for at least 2 weeks.
At least five of the following symptoms have been present during the same 2 week depressed period.
1. Abnormal depressed mood (or irritable mood if a child or adolescent) [as defined in criterion A].
2. Abnormal loss of all interest and pleasure [as defined in criterion A2].
3. Appetite or weight disturbance, either:
i. Abnormal weight loss (when not dieting) or decrease in appetite.
ii. Abnormal weight gain or increase in appetite.
4. Sleep disturbance, either abnormal insomnia or abnormal hypersomnia.
5. Activity disturbance, either abnormal agitation or abnormal slowing (observable by others).
6. Abnormal fatigue or loss of energy.
7. Abnormal self-reproach or inappropriate guilt.
8. Abnormal poor concentration or indecisiveness.
Also physical symptoms - Patients ‘feel ill’, ‘malaise’ (like flu) fatigue, ‘TAT’ (tired all the time), washed-out, heaviness, aching, headaches and pain in trunk and limbs.
When depression is severe (c 1% diagnosed depression) and associated with sleep deprivation - may develop psychotic features.
Delusions of worthlessness, guilt, sickness, poverty, ‘nihilism’.
Hallucinations - voices of a derogatory, accusatory nature.
Severe slowing of speaking and moving.
Stupor, dehydration, starvation - potentially fatal.

Epidemiology
Prevalence MDD – 5-10 percent – more than 100 fold increase since 1950s
If untreated - cases psychiatrists see usually spontaneously recover within several months, majority have a relapse within 10 years.
Around 10% patients who have serious depression (psychiatric contact) will commit suicide - but suicide rate probably not elevated in primary health care depression.

Aetiology
No single cause, probably many causes and sub-types.
Main theory is some kind of brain deficiency in amines – dopamine, noradrenaline and/ or serotonin.
Life events
Malaise due to immune system activation

Treatments
Supportive psychotherapy/ counselling
Psychological therapies - esp CBT
Drugs - antidepressants – Tricyclics; SSRIs; Monoamine oxidase inhibitors (MAOIs) – phenelzine; other drugs not in these classes - eg trazodone, venlafaxine (effexor); St John’s Wort - Hypericum
SSRIs for milder, outpatient depression/ anxiety - tricyclics for moderate to severe hospital depression.
ECT for severe depression especially with psychotic features or danger of suicide or starvation/ dehydration.

Mechanism
Nowadays more general ‘amine hypothesis’ - 5-HT is the most fashionable cause. Idea of brain deficiency of amine NT, corrected by drugs.
Both tricyclics and SSRIs are amine re-uptake blockers, MAOIs block enzyme that breaks down amines.

Seasonal Affective Disorder – SAD

Eagles JM, British Journal of Psychiatry. 2003; 182: 174-6
Lam RW. Primary Care Psychiatry. 1998; 4: 63-74
www.mentalhealth.com under Cyclothymic Disorder

Winter depression/ blues, linked with treatment with bright light therapy given in the mornings.
Increased incidence of depressive symptoms/ major depressive disorder during winter months (although ‘seasonal’ does allow for other times of the year).

Typical clinical picture varies in severity in a continuum, with symptoms such as:
1. Fatigue & Reduced motivation
2. Excessive sleeping (hypersomnia)
3. Increased appetite (carbohydrate craving) and weight gain
4. Irritable mood
5. Reduced sociability

Some doubt about the validity of this disorder in some quarters, since depressive symptoms are common and by chance could occur in winter. Some people regard it as hypochondriacal. It seems to be completely accepted professionally and socially in high latitude countries such as Scandinavia and Canada/ Alaska.
But SAD has a high level of biological plausibility given the profound effects of light and seasons on animal behaviour and evolution.

Humans evolved in Africa between c30 degrees north and south
Eg. Texas 30 degrees North, Naples 40, Canada 40-50, Newcastle 54, Iceland 65 Arctic Circle 66.5.

Pathology
Main theory is that people with SAD are unable to adapt to shorter photo-period in winter.
Circadian phase shift – daily hormonal and neurotransmitter rhythm gets delayed by late rising and insufficient light.
Some people think this is related to the hormone melatonin XS melatonin (usually suppressed by light).
Other theories relate to serotonin dysregulation – has seasonal variation in normal metabolism.

Epidemiology
Some inconsistencies in literature – often use Seasonal Pattern Assessment Questionnaire (SPAQ) which probably gives false positives.
Prevalence varies from 0-10 percent – worse in winter.
Commoner in women, especially in childbearing years

Latitude
SAD prevalence seems to be associated with latitude.
But relationship between SAD and latitude may plausibly have a threshold, and need not be a straight-line relationship (this seems not to have been taken into account in studies).
Rosen at al (1990) demonstrated a gradient in SAD going up the east coast of the USA from Florida to New Hampshire (27-43 degrees North).
Evidence of acclimatization in individuals and SAD seems worse for people who migrate to extreme latitudes.
Also evidence of longer-term adaptation of populations who have been at extreme latitude for many generations (eg Iceland) – seem to have lower prevalence than otherwise expected for latitude (eg Icelandic Winnepegians versus non-Icelandic. ie. SAD seems to vary by ‘ethnicity’.
This implies some genetic element – and SAD probably heritable.

Treatment
A proportion of people get better with time – c. one third?

Light therapy
Seems very effective, although it is hard to compare with placebo
Indoor lighting c 100-400 lux (evening at home - office)
Outdoor cloudy winter day – 4000 lux
Outdoor bright sun – 40 000 lux plus
Treatment with ‘light boxes’ usually (in trials) 2500 lux for 2 hours/ 10 000 lux for 30 mins.
‘Light visor’ efficacy seems not to benefit from high intensity light - ? close proximity of light source
Dawn simulators go from darkness to c 400 lux.

Administered in the morning – tends to support the idea of circadian rhythm abnormality, since bright light would cause ‘phase advance’ – make circadian rhythm occur earlier in the 24 hour cycle.
Dawn simulation alarm clocks also seem to work (while the person sleeps) – easier to integrate with a normal life (esp with hyper-somnia as a symptom)
Problem of funding trials of non-pharmacological treatments, and blinded controls.
Antidepressants - SSRIS are widely used and may be effective
Or can ‘go south’ for the winter – that works within a few days, but only for as long as you stay, relapse about a week after return…

Normal SAD sufferers
Would expect a continuum, and for this to be shifted by latitude (interacting with other factors such as age and weather).
Leading to ideas for combating this in extreme latitudes – eg brighter lighting in hospitals and workplaces
Outdoor/ bright light exercise is another factor


PSY 3007- Lecture 6 - Tricyclic antidepressants and ECT

Tricyclic antidepressants (name refers to chemical structure).

Imipramine, amitriptyline, clomipramine (mainly serotonin effect), desipramine (mainly norepinephrine effect), lofepramine is probably current favourite due to safety.

Psychological action
Poorly understood, apart from Prozac, drugs are not even well known
Considered generally to be ‘mood normalizers’.
Not tranquillizers, not addictive, not abused, not significantly mood elevating/ euphoriant/ activating.
Supposedly do not significantly affect mood of non-depressed.
Many patients aware only of side effects (sedation, dry mouth, nausea), not the therapeutic effect which is slow and gradual
Perhaps their core action is to treat physical symptoms of depression, not the psychological symptoms - ie affect body primarily, rather than brain (my theory).
Threshold dose in order to be effective, and tricyclics and MAOIs dangerous in overdose

Mechanism
Catecholamine hypothesis 1965 Schildkraut - emphasized deficiency of norepinephrine action.
Nowadays more general ‘amine hypothesis’ – includes 5-HT is the most fashionable cause, or possibly dopamine.
Idea of brain imbalance of NT, corrected by drugs. That certain types of NT are responsible for certain aspects of behavior.
Antidep.s act (but weakly) on receptors in brain.
In many people depression, is a chronic illness, and drugs do not cure it but alleviate symptoms - so drugs may need to continue. Also prone to relapse.



Positive and Negative Affect (ideas of David Watson, U of Iowa)
Positive Affect: Happiness, Interest, Motivation, Alertness, Self-confidence
Negative Affect: Subjective distress, fear, anxiety, irritability, loneliness, guilt, disgust, hostility.

Two kinds of depression:
Both exhibit low mood/ sadness
Depression with loss of energy and motivation, and anhedonia.
Depression with anxiety, guilt, irritability and fear.

Depression with loss of energy best treated with drugs that increase synaptic dopamine/ NE – ie MAOIs such as phenelzine or moclobemide, tricyclics such as desipramine, or other unusual drugs such as reboxetine or more ‘psychostimulant’ drugs such amineptine.
Depression with anxiety best treated with drugs that increase synaptic serotonin – ie. SSRIs

General clinical effect -
Act rapidly on physical symptoms
- improve sleep and appetite reliably,
- analgesic effect
- – treats some unpleasant feelings such as fatigue (‘run down’ ‘tired all the time’), heaviness, dullness, aches.
Act slowly to improve mood - 2-6 weeks.
Tricyclic side effects
- weight gain
- dry mouth, constipation,
- sedation,
- impotence or difficult orgasm
- Dangerous in overdose (not lofepramine).


ECT – electroconvulsive therapy or ECS – electroshock therapy

The History of ECT - Edward Shorter - Psychiatric Times. February 2004
ECT – textbooks
http://www.americanscientist.org search site for ‘fink’
hedweb.com/bgcharlton - delirium and psychotic… anti-delirium theory…

Use of electrical current passed through the brain to induce a ‘grand mal’ general epileptic seizure.

Describe procedure
General anaesthetic – patient asleep
Muscle relaxant – patient ventilated
Application of electrical current via moistened electrodes on scalp
Epileptic seizure usu. tens of seconds
Anaesthetic and muscle relaxant wears off – patient wakes, goes to rest and recover

Describe therapeutic aspect
Is benefit from:
1. epileptic seizure - seizure ‘re-sets’ brain?
2. passage of electrical current - current ‘re-sets’ the brain.
3. Both

Indications
1. psychotic depression
2. mania
3. acute schizophrenia
4. delirium
5. Parkinson’s disease.

Side effects
For about an hour immediately after awakening – ‘acute confusional state’ of disorientation, transient memory loss, and headache. Laying-down of new memory is impaired. Longer term memory problems – but memory problems due to the reason for which ECT is given – eg severe depression, mania etc.
Severity of memory problems is greater with more treatments and less if only one side of the brain is treated (usually R – non-language function).
Learning new information is impaired affected for c. several weeks after ECT course, then returns to normal.
Some patients report subjective LT impairment in memory function especially for events that before ECT (retrograde amnesia) – as if recently laid-down memories were ‘wiped’ by ECT.

Mechanism of action – some theories
Not known – and no accepted theory (not even a false one) – this limits confidence in use.
NT, amine imbalance in some subtle way – or receptor changes?
Hormones – Max Fink suggests hypothalamus releases mixture of hormones
ECT alleviates delirium caused by sleep disruption.
ECT-induced fit may promote natural sleep. Plus electrical current may suppress abnormal brain waves, and allow normal ones to be re-established – analogous to cardioversion.




PSY 3007 Session 7 - Psychological treatments - behavioral and cognitive therapies

References - Textbooks of Clinical Psychology

Many types of psychological treatment for psychiatric illness - including psychoanalysis/ psychodynamic psychotherapy, many forms of ‘counselling’. Often very ambitious, aiming at a profound transformation of personality.
But most of these appear to be elaborate placebos, in that they have no measurable specific effect related to the background theory or training of therapists.
With regard to effectiveness, a professional and trained psychoanalyst, psychotherapist or counselor is no better at treating eg. depression than a randomly selected person.
But also ‘Psychological therapies’ which are distinctive in having underpinning in psychological theories, and evidence for specific effectiveness in specific conditions
These therapies produce, on average, better results than T,D or H when used appropriately.
They tend to be short-term, focused, goal-oriented – not transformative.
The most important are Behavioral Therapy, and Cognitive Therapy - and their combination - CBT.

Behavioral Model and Behavioral Therapy
Theory - Abnormal behaviors are learned via standard learning processes
eg. Classical conditioning, Operant conditioning, Modelling.
Treatment of abnormal behaviors involves replacing them with new behaviors learned by the same mechanisms
In simple words, in BT a person practices doing the kind of things that they fear doing or try to avoid.

· eg Snake phobia - Analyzed in terms of Exposure to stimulus, and response to stimulus.
· Someone sees a snake, becomes anxious, runs away, anxiety is reduced - behavior is reinforced, phobia is maintained.
Behavioral therapy, the idea is that the client learns new behavior, breaks a vicious cycle of maladaptive learning. eg.
Control exposure to stimulus, graded hierarchy of exposure to snakes - systematic desensitization. At each stage in exposure, wait for anxiety level to diminish ‘extinguish’, then move on to next level.
Control response to stimulus - do not run away, wait for anxiety level to subside ‘extinguish’.
Plan of treatment - highly focused, agreed. Agree on exposure hierarchy - think about snake, picture of snake, toy snake, video of snakes, look at tiny snakes, handle tiny snakes…
Exposure in therapy sessions, ‘homework’ (carry pictures, toys of snakes).
Can continue therapy intermittently to maintain gains.


Cognitive Model and Cognitive Therapy
People are regarded as information-processors, as with cognitive psychology.
Emotions and behaviors are a consequence of information processing (perceptions-processing-behavior)
Changing the way you process information can change emotions and behaviors.

CAUSE of symptom: Abnormality is due to maladaptive ways of processing information - misinterpretations.
eg. If I have a headache, then I have a brain tumor.
Negative beliefs schemas - about oneself, about other people, the world.
Schemas are general patterns of interpretations about ‘how things work’.
‘I start well but then fail’,
‘people like me at first then realize I am boring’.

Treatment
· ‘Collaborative empiricism’ - collaborative, worked out between therapist and client, empiricism - things are tried out in sequence to see if they are effective.
· Try to establish the key errors in information processing that lead to low mood. Identification of eg: negative thoughts, triggers, emotions.
· Generate plausible alternative explanations - the client should generate these in a hypothetical spirit.
· Identify and challenge maladaptive processes - rules, assumptions, beliefs.
· Behavioral experiments and monitoring for behavioral change often as homework.

In other words, with CT the therapist rationally discusses patterns of thinking and emotions, and elicits suggestions of alternative plausible more adaptive patterns.

Beck’s Cognitive Therapy for depression (really CBT)
Depression is caused by negative thinking - negative cognitive triad:
1. about oneself,
2. the world and
3. the future .

Unclear how this kind of cognitive abnormality or bias arises – tends to be accepted as the starting point of therapy.
Therapist looks for thinking ‘errors’ (maladaptive habits) –
eg.
· Over-generalization,
· dichotomous thinking,
· mind-reading.
Challenges these errors, usually by asking for justification or critique.
Generates alternatives, usually by asking client to do so, perhaps in a formal way.

Conclusions
CBT - good evidence from treatment trials of effectiveness in depression and other focused conditions (eg delusions).
When it works probably has long-term benefits – claimed to be ‘cognitive re-structuring’, or at least change of habitual style of thinking.
Indeed, Cognitive Therapy is a kind of indirect persuasion or ‘soft sell’ as it is termed in advertising. Guide the client to believe they have reached pre-determined conclusions for themselves, which is more convincing.
But research patients highly selected and relationship between theory, practice and mechanisms of change are not clear - eg cognitive changes occur with antidepressants.

PSY 3007-8 Mania
Muzina DJ et al 2002. Epilepsy Research 50: 195-202

MANIA
Bipolar disorder, manic-depressive disorder.
A long term illness in which person has periods (weeks/ months) being ‘high’/manic and periods being low/depressed
Bipolar refers to these two ‘extremes’

Case history - young adult man or woman, episode in which feels more energy, increased activity, several days without sleep, goes completely crazy and scary, but no insight. Ends up heavily sedated in psychiatric hospital - usually rapid recovery and complete return to normal (though without always getting insight).

Not a concept in common use - nearest would be John Cleese as Basil Fawlty, Robin Williams in Good Morning Vietnam, or Eddy Izzard in full flow.

Manic mood: ‘high’ - elated, irritable, hostile
Core Features of Hypomania (less than mania)
1. Increased energy/ activity - decreased desire for sleep
2. Hyperactivity including over-talkative, racing speech
3. Poor Concentration or Attention
4. Inflated Self-Esteem or Grandiosity
5. Reckless or Impulsive Behavior

Associated: uncharacteristic behaviours
- Economic Problems, impulsivity, novel illegal or criminal behaviour, promiscuity or sexual aggressiveness, physical violence, alcohol/ drug abuse.
React badly to thwarting (humor the manic!)

Several days without any sleep may precede exacerbation to more severe variant of Mania.
Mania is a psychotic illness
Delusions & Hallucinations, (mood congruent)
Grossly disorganized speech or behaviour
Overactivity without treatment (olden days) may lead to exhaustion, collapse, even death.

Prognosis
90 percent chance of further episodes – usually few years between them
c10 episodes in life
Usually full recovery between episodes
But in 5 years maybe 5 percent have died, suicide is common.
Tend to become more frequent with age (rapid cycling)

Treatment
Lithium carbonate
Mood stabilizers – carbamazepine, sodium valproate/ valproic acid
Neuroleptics
Benzodiazepines
BUT – most patients are ‘non-compliant’ - do not take their treatment
Pateints may need supervising/ watching to prevent a breakdown building
NB- antidepressants, especially tricyclics, sometimes seem to provoke mania.


Epidemiology
c1 percent lifetime prevalence – c 10 percent or more in first degree relatives.
Same in both sexes

Cause - probably genetic predisposition (plus acute stress), often runs strongly in families eg Amish, other migrant groups.
c40 percent concordance in MZ twins (but not 100%), c5 percent in DZ twins.
May be some advantages in slight hypomania, commoner in creative types and emigrants.

Insight
Manic patients usually lack insight. Do not feel ill, react angrily to suggestions that they are, will not take treatment, usually require compulsory admission and treatment.
May never admit they have been ill – explain it all as a mistake, a misunderstanding
Usually reluctant to take preventive treatment
Therefore an almost unique disorder in that it is diagnosed on the basis of abnormal behavior as defined by other people
Why such poor insight? Because manic patients often feel good, more energetic, higher self esteem – all subjectively interpreted as a consequence of good health, not of illness.


Treatments of mania
1. Lithium
And a group of anti-epileptic / anti-convulsant drugs
2. Carbemazepine
3. Sodium Valproate/ Semi-sodium valproate / Divalproex sodium/ Valproic Acid
4. Neuroleptics

Lithium
One of the most important psychiatric drugs
An ion, prescribed as a salt - lithium carbonate.
Initially recognized as a calming, or tranquilizing drug - used as a sedative in acute mania. Discovered 19th century lithium water (naturally occurring, eg Perrier, Vichy - used as treatment for gout
Then again discovered mid 20th as sodium substitute in salt-free diets – but caused some deaths so withdrawn.
Cade (Australia) working on urine of manic patients in guinea pigs, found that lithium seemed to protect against toxicity and sedate the GPs. But still problems of toxicity.
Re-launched in 1960s esp by Dane called Schou – with blood level monitoring.

1. Now lithium is used mainly as prophylactic (preventive) for manic depressive illness - prevents recurrences of both mania and depression.
2. Unknown mode of action.
3. Narrow therapeutic range. Ineffective in low doses, toxic in high doses – must monitor blood levels.
4. Dangerous in overdose, toxic to fetus.
5. Often bad side effects - tremor, dry mouth (thirst), weight gain. Seems to make people feel dulled and unresponsive - or they may miss the excitement of mania.
6. Probably, lithium maintenance significantly reduces suicide rate, but withdrawal significantly increases it.
Therefore in 1980s psychiatrists began trying out different type of drugs – the anti-epileptic ‘mood stabilizers’.

Mood Stabilizers
So-called ‘mood stabilizers’ are anti-epileptic drugs used for two purposes. But anti-epileptics don’t help MDD as a class, only certain types - and these seem to operate in different ways.

1. Treatment of manic episodes
2. Prevention of mania +/- Depression in bipolar disorder
3. Reduction of mood swings/ aggression/ irritability

Carbamazepine
Used in controlling aggression and some types of pain syndrome – trigeminal neuralgia.
Mainly effective in controlling mania – probably works as a kind of tranquillizer.
Rare nasty blood side effects
An anti-irritability anti-manic agent – alternative to neuroleptics.

Sodium Valproate/ Valproex/ Valproic Acid
Used in children as anti-epileptic.
Sedative action, useful at controlling and preventing mania – but not depression.
But side effects include XS sedation, fatigue, weight gain, hair loss
A sedative anti-manic agent.

Neuroleptics
Given to control agitated behaviour in acute mania. May also be given to prevent MD episodes, especially mania. Sometimes given by long-acting injections. Increasingly used in children who are increasingly diagnosed as bipolar.

Probably carb, valp and lithium are not truly preventive, but actually acute symptomatic treatments. They are like continuous acute treatment. Analogy: taking paracetamol every day does not prevent paid, but continuously treats pain (if present).
But the sedative action may promote sleep, and prevent the positive feedback cycle that leads from a high mood to full blown manic episodes


PSY 3007-9 - Schizophrenia and Psychotic Symptoms

Sims A, Symptoms in the mind
My book chapter- theory of mind delusions and bizarre delusions

Schizophrenia
The classic form of ‘madness’
Almost certainly not one ‘disease’ with one cause - a collection of diseases that produce broadly characteristic symptoms.
Nature of such diseases may have changed over time – eg. at various points and places in past hundred years mania, delirium from various ‘malnutrition’ diseases, and late-stage syphilis may all have been diagnosed as schizophrenia.

Clinical features
1. Hallucinations - hearing voices, eg. running commentary, voices discussing third person, spoken thoughts
2. Delusions - bizarre false beliefs
3. Thought-disorder - weird illogical, interrupted speech
4. Catatonia - illogical, strange movements
5. Supposedly - Negative symptoms - asocial, lack of drive, blunted emotions. However, these are also side effects of neuroleptic drugs used for treatment – probably negative symptoms are usually iatrogenic.

Epidemiology: c 1 percent of population, usually insidious onset late teens early twenties, both sexes equivalent. Some people say this is similar is all societies, but actually varies several-fold and has different prognosis at different times in history and in different countries today – maybe different mixes of diseases, and different effects of treatment.

Give case history
Chronic, usually progressive with relapses and remissions
May slide down social scale, seldom sociable or creative
Evidence that the prognosis has become worse over recent decades, and is worse in developed countries. This could be caused by changes in the nature of patients diagnosed as schizophrenia (eg that the causes in the past differ from causes nowadays).
Also linked to the increased usage of neuroleptic drugs, and withdrawal from these drugs – both of which may also lead to increased suicide rate in this group.

Treatment –
Acute – as for mania – sedation using benzodiazepines (lorazepam, midazolam) or antihistamines such as promethazine; and neuroleptics/ antipsychotics such as haloperidol or droperidol.

Chronic – Social
Role of CPN.
Hospitalisation, Rehabilitation, Day Hospitals, Supervised Housing.
Neuroleptic drugs (next week). Probably prevents relapse in some people; but stopping them causes relapse in most people.

Causes
Not known, probably because many diseases and many causes
Usually considered to be a brain disease. Suggestion that dopamine activity may be excessive (related to action of neuroleptic drugs and amphetamine psychosis).
Some evidence for genetic transmission, although there is reduced fertility. Maybe a spontaneous genetic mutation or a range of mutations that affect brain in general way.
Some cases may be due to viral infection or trauma when brain is developing.
Some cases may be a dementia-like process.
Almost certainly, schizophrenia is not one thing nor does it have one cause, but is a variety of causes and disease processes with some common features.
Psychotic symptoms
Madness - qualitatively abnormal behavior (either for group, or for that individual).
Disorganised and agitated behaviour without insight.
Reality judgment (‘reality testing’) is significantly disturbed (eg. bizarre/ impossible delusions).
Not understandable from personality and circumstances.
Refers to symptoms such as hallucinations, delusions - also incoherent speech/ thought-disorder.

Hallucinations
Sensory perception when there is no real object to perceive - a false perception (NOT a distortion of a real perception or a misinterpretation). Appears to the patient as a normal sensory experience, indistinguishable from real.
Any sensory modality - hearing, vision, touch, taste, smell.
Occur in schizophrenia, mania, depression, chronic alcoholism, delirium, dementia, also hypnagogic hallucinations.
Depression and mania – auditory, mood congruent themes.
Bodily sensations (heat or cold, touching, fluid inside, tingling, formication). Can be linked to delusions of control - hallucinatory experience and a false belief - sex with both Kennedy brothers all the time.
Delusions of smell or taste - eg smell a poisonous gas or taste a poison, or depressive (rotting, disgusting smell etc).
Delusions
False, unshakeable and dominating idea, out of keeping with personal and cultural background.
Feels indistinguishable from a true belief - only recognized by other people.
Some delusions are primary, apparently not derived from other symptoms.
Others are secondary - ie false beliefs to ‘explain’ hallucinations, or mood changes.
Some delusions are bizarre, others are plausible but untrue.
Some delusions are associated-with, or based-on, illogical reasoning, others occur in context of normal reasoning.
Schizophrenia - delusions typically of ‘self-reference’, usually persecutory, may be bizarre and illogical (budgie).
Depression and Mania delusions are mood-congruent

Causes?
Unknown – some ideas…
1. Dopamine hypothesis - symptoms may be improved by neuroleptics. But this may instead merely suppress behaviour in response to symptom; change attitudes to hallucination – indifferent to them.
2. Auditory hallucinations: Sub-audible vocalizations (whispering). Sometimes can record with throat microphone.
3. Auditory hallucinations (Despite definition) may involve misinterpretation of environmental sounds (eg TRESS repeated) - May be suppressed by other noise (Walkman) or earplugs.
4. Delusional disorder - delusions of persecution, jealous delusions of sexual infidelity - Charlton ‘theory of mind’ delusions - mistaken inference about the intentions of others plus vulnerable personality - eg low self-esteem and jealousy. Implies treatment by rational persuasion – CBT etc.
5. Charlton & Kavanau - hallucinations and delusions caused by delirium secondary to sleep disturbance - ie all hallucinations may be ‘hypnagogic’ - like ‘waking dreams’. May be treated with sedation to allow sleep, perhaps ECT for severe cases.
6. Bentall - that hallucinations caused by faulty judgement of the origin of perceptions. Meta-cognitive ability to discriminate self generated from external sources of information.
7. Bentall has suggested that in patients with persecutory delusions there may be faults in reasoning - eg. tendency to jump to conclusions based on insufficient evidence. Fits with fact that some delusions can be improved by cognitive-behavioral therapy.


PSY 3007 - 10 Neuroleptics

Whitaker R. The case against anti-psychotic drugs. Medical Hypotheses 2004; 62: 5-13.
Charlton BG – book and neuroleptics papers.

Neuroleptics - major tranquillizers, anti-psychotics
eg chlorpromazine (first), haloperidol (strongest), clozapine (atypical)
Used mainly to suppress psychotic, aggressive or in some way socially inappropriate behaviour.
Most associated with treatment of schizophrenia, both acute treatment of breakdowns, and chronically in order to prevent further breakdowns.

Behavioural control
Before neuroleptics behaviour was controlled – in psychosis and otherwise – using sedative drugs such as bromide, barbiturates, paraldehyde, and antihistamines.
These made patients sleepy – less motivated to be violent etc. Aslo, sleep may have a therapeutic role, especially if sleep deprivation has been a causal factor in producing the symptoms.
Sedatives may induce dependence, barbiturates were addictive.
Related sedative anti-histamines available OTC for anti-emetic, anti-allergy, cough suppressant, or as hypnotics or anti-histamine eg. promethazine/ Phenergan, trimeprazine/ Vallergan, diphenhydramine / Nytol & Benylin.
Neuroleptics discovered – some were sedative, but they controlled behaviour even when the sedation had worn off, and some were not sedative but still apparently ‘calmed’ agitation.
Sedation still remains a very important mode of controlling behaviour – most acute patients continue to receive eg benzodiazepines or sedative anti-histamines, or modern very sedative ‘atypical’ neuroleptics.
But the discovery of neuroleptics brought something new to behavioural control

Discovery of neuroleptics
Manufactured from antihistamines – promazine modified with addition of a chlorine to make chlorpromazine – the first neuroleptic.
Discoverers were French: Delay, Deniker, Laborit - generally consider major therapeutic breakthrough, but no Nobel, mainly due to disputes between discoverers.
Synth 1950, given to humans 1952.
Rapidly spread to be vastly prescribed and profitable – sometimes every patient in a massive hospital would be tried on it/.
‘Neuroleptic’ means ‘nerve-seizing’ – seizes and holds the nervous system in a constant state, ie. blunts emotions

Major therapeutic effect of neuroleptics
1. Induces state of psychic indifference (tranquillization) by blunting of emotion (neuroleptic).
2. Anti-agitation - not getting worked up (rather than getting sedated-down towards sleep)

But not truly ‘Anti-psychotic’, when used for treatment of hallucinations, delusions, thought-disorder. Usually stops people responding to psychotic symptoms, making them ‘indifferent’ to symptoms, rather than actually alleviating the psychotic symptoms.

Clinical uses
Used in schizophrenia, mania, psychotic major depressive disorder, agitation from any cause, and to suppress undesired behavior in demented and deliriuous old people – eg elderly homes, and in non-psychotic violent people eg. in prisons.
May be given as a long-acting depot injection. Various formulations – some work for c 3 days others for about a month.
In very high doses – produce immobilization – ‘chemical straitjacket’ (but inner turmoil).

General view - neuroleptics suppress symptoms, do not cure disease.
Patients who take the drugs ‘cleverly’ (as required) feel better and do not suffer any more hospital admissions.

Side effects
Dysphoric – make people ‘feel bad’, patients hate taking them – not abused. Negative symptoms - demotivation, loss of enjoyment, lack of energy and drive.

Akathisia – inner turmoil, restlessness and agitation
Generate abnormal movements – Parkinson’s disease or Parkinsonism – tremor, difficulty in moving etc. Behavioural control effect is dose related and related to dopamine blocking potency. Cannot get benefits without side effects.
Indeed, essentially neuroleptics control behaviour by inducing Parkinsonism which includes emotional blunting and indifference. By inducing indifference people are less motivated to behave, general reduction in motivation and drive affects both pathological psychotic symptoms and normal human motivations.
Long term high dose use may create a permanent kind of Parkinson’s disease termed Tardive Dyskinesia may be permanent – presumably due to toxic effect on nerve cells.
Dependence with long term usage, so that it may be difficult to stop taking the drug without provoking an agitated psychotic breakdown. More prone to relapse than if hadn’t taken them in the first place – probably major factor in worse outcome of ‘schizophrenia’ in modern societies – neuroleptic damage and dependence.

Atypical Neuroleptics
Fewer Parkinsonian effects, weaker neuroleptics
Weight gain – diabetes and similar disorders
Sedation
Increased death rates from variety of causes including diabetes

Mechanism of action
Dopamine blocking by neuroleptics – reduces drive and emotional responsiveness - libido.
Act on basal ganglia – control of emotions and fine muscular coordination
Atypical neuroleptics clozapine, reserpine, olanzepine.
Different chemical mode of action - also act on blocking serotonin - 5-HT2 receptors - esp clozapine and the atypical neuroleptics. Serotonin receptor blockade seems to be related to sedation and weight gain.

Future?
For many decades have been regarded as one of the major therapeutic breakthroughs ever. But arguably neuroleptics overall do much more harm than good.
The behavioural control effect seems to be achieved by making patients Parkinsonian, indifferent and demotivated. Achieves its social goal, but for the individual emotional blunting and dysphoria may profoundly reduce the quality of life. If patients then become dependent then the situation may be permanent.

Conclusion - ?
Minimize neuroleptic prescription except as a last resort.
Use sedatives and seek alternative substitutes.