Psychopharmacology 115

You are asked to review a man on a hospital ward with hemochromatosis who has been observed to be low in mood. On review of his blood results you note significant hepatic impairment. You history and examination confirms that he is depressed. Which of the following medications would be indicated to manage his depression? 



Haemochromatosis is an inherited disorder in which iron levels in the body slowly build up over many years. If left untreated, the extra iron is deposited in the body, usually around organs, such as the heart and liver and can lead to both liver and heart failure. Once diagnosed, hemochromatosis is treated by phlebotomy to rid the body of excess iron and to maintain normal iron stores.

Hepatic impairment


Patients with hepatic impairment may have:

  • Reduced ability to metabolise (toxicity and enhanced dose related side effects)
  • Reduced ability to synthesize plasma proteins (toxicity from high protein bound drugs)
  • Reduced hepatic blood flow (elevated levels of drugs subject to first pass metabolism)

The following table (Maudsley Guidelines 2012) lists the drugs recommended in hepatic impairment:

Drug GroupRecommendations
AntipsychoticsHaloperidol
Amisulpride
Sulpiride
AntidepressantsImipramine
Paroxetine
Citalopram
Mood stabilisersLithium
SedativesLorazepam
Oxazepam
Temazepam
Zopliclone 3.75mg (with care)

The Maudsley Prescribing Guidelines 11th Edition 2012.

Psychopharmacology 114

Which of the following metabolic changes is associated with QTc prolongation?


QTc prolongation


In addition to psychotropic drugs, there are a number of additional risk factors for QTc prolongation to consider.

QTc prolongation is an indicator of risk of torsade de pointes and increased cardiac mortality.

Risk factors for QTc prolongation
Long QT syndrome
Bradycardia
Ischaemic heart disease
Myocarditis
Myocardial infarction
Left ventricular hypertrophy

Hypokalaemia
Hypomagnesaemia
Hypocalcaemia

Extreme physical exertion
Stress or shock
Anorexia nervosa
Extremes of age (old or young)
Female gender

You should also be aware that a number of non-psychotopic drugs can cause QTc prolongation.

ClassExamples
AntibioticsAmpicillin
Erythromycin
AntiarrthythmicsAmiodarone
Sotalol
AntimalarialsChloroquine
Quinine
OthersMethadone
Tamoxifen
Amantadine

Above tables adapted from the Maudsley Guidelines

Psychopharmacology 113


Electroencephalography


Electroencephalography is the recording of electrical activity along the scalp produced by the firing of neurons within the brain. 

In clinical contexts, EEG refers to the recording of the brain's spontaneous electrical activity over a short period of time, usually 20-40 minutes, as recorded from multiple electrodes placed on the scalp. 

It is mainly used as a test to rule out organic conditions. Research has showed it to be of use in differentiating dementia from disorders such as metabolic encephalopathies, CJD, herpes encephalitis, and non-convulsive status epilepticus. EEG may also help to distinguish dementia from pseudo-dementia. Similarly EEG has a role in distinguishing possible psychotic episodes and acute confusional states from non-convulsive status epilepticus.

Not all abnormal EEG's represent an underlying condition, a study of trainee pilots found 0.5% (n=69) to have epileptiform discharges and only 1 of them went on to develop epilepsy. EEG's are affected by psychotropics, this generally manifests as generalised slowing but spike activity is also seen.

Occasionally EEG abnormalities are triggered purposely by the means of activation procedures. These procedures include; hyperventilation, photic stimulation, certain drugs, and sleep deprivation.

Quantitative EEG is essentially an EEG used with a sophisticated computer that is able to do a more detailed analysis of the trace.

Specific wave forms are seen in an EEG and you need to be familiar with these.

TypeFrequencyNormally foundNormally seen in
Delta1-4HzFrontally in adults and posteriorly in childrenSlow wave sleep and in babies. Should not be present when awake, when present if awake this strongly suggests pathology
Theta4-8HzGeneralisedYoung children, drowsy and sleeping adults, with certain medications, meditation. Small amount seen in awake adults, excessive amount when awake may indicate pathology
Alpha8-12HzPosteriorlyWhen relaxed and when the eyes are closed (whilst awake)
Beta12-30HzFrontallyWhen busy or concentrating
Sigma12-14HzFrontal and central regions(aka sleep spindles) Bursts of oscillatory activity that occur in stage 2 sleep. Along with k-complexes they are the defining characteristic of stage 2 sleep
Gamma30-100HzNo specific areasMeditation

Certain conditions are associated with specific EEG changes (see below)

ConditionEEG findings
CJD (sporadic only, does not apply to variant)Early on there is non specific slowing, later periodic biphasic and triphasic synchronous sharp wave complexes superimposed on a slow background rhythm
Huntington'sLow voltage EEG, in particular no alpha (flattening)
DeliriumDiffuse slowing, decreased alpha, increased theta and delta
Delirium tremensHyperactive trace, fast
Alzheimer'sReduced alpha and beta, increased delta and theta
Petit mal epilepsy (absence seizure)Generalised, bilateral, synchronous, 3Hz (3 waves per second) spike and wave pattern
Generalised epilepsySharp spikes, 25-30Hz
Partial epilepsyFocal spikes
Myoclonic epilepsyGeneralised spike and wave activity
EncephalopathyDiffuse slowing
Normal agingDiffuse slowing, which can be focal or diffuse, if focal most commonly seen in the left temporal region

Medications can have important effects on the EEG and you must be aware of these.

Drug classEffect on EEG
Antipsychotics (typical)Decreased beta with Increased alpha, and delta, haloperidol least effect
Antipsychotics (atypical)Varied effect, clozapine most significant effect
AntidepressantsReduce beta, increase all others
AnticonvulsantsNo effect
LithiumSlowing
BenzodiazepinesIncrease beta, decrease alpha
BarbituratesIncrease beta

Drug of abuseEffect on EEG
Stimulants (cocaine, nicotine)Increase alpha
Depressants (alcohol, opioids)Decrease alpha
CannabisIncrease alpha

Psychopharmacology 112


Prescribing in the elderly


Older people's bodies are different to those of younger adults and this affects how they handle medication. Additionally they are often on a range of other drugs so interactions are an issue.

Both pharmacokinetics and pharmcodynamic differences apply.

Pharmacokinetics 

Changes in distribution, metabolism, and excretion are important.

Absorption 

In old age there is reduced gastric acid secretion. This is accompanied by decreased gastric motility, and reduced surface area available for absorption. Pharmacokinetic studies on the effect of ageing on drug absorption have provided conflicting results. While some studies have not shown significant age-related differences in absorption rates for different drugs, the absorption of vitamin B12, iron and calcium through active transport mechanisms is reduced, whereas the absorption of levodopa is increased.

Distribution

There is a relative reduction of body water to body fat (the elderly have more fat and less water) as the body ages which results in an altered distribution of lipid soluble drugs. Older people also have less albumin. These changes result in increased blood levels for water soluble drugs, decreased levels for lipid soluble drugs (increased volume of distribution), and a greater unbound free fraction (increased amount of active drug). As people age, the half-life of a lipid soluble drug increases.

Metabolism

Hepatic metabolism of drugs decreases with age as a consequence of reduced hepatic blood flow and reduced enzyme activity.

Excretion

The kidneys become less effective with age (by 65, 35% of renal function is lost, and by 80, 50% is lost). Serum creatinine and urea is often used to estimate renal function but can be misleading in the elderly as they have less muscle and so produce less creatinine. 

The e-GFR is a tool that can be used to estimate renal function in the elderly.

Drugs that are primarily excreted by the kidneys (e.g. lithium and sulpiride) will tend to accumulate in the elderly and so small doses may be needed.

Pharmcodynamics 

Receptor sensitivity tends to increase during old age and so this group tends to require smaller doses. It is generally recommended that you start with half of the usual adult dose and go on from there. This increase in sensitivity contributes to an increased incidence of side-effects in the elderly.

Older people tend to take longer to respond to treatment (the therapeutic response is delayed).

Above compiled from:

Seminars in clinical psychopharmacology, 2nd Edition
Maudsley Guidelines 11th Edition
Kaplan and Sadock's Synopsis of Psychiatry 11th Edition

Psychopharmacology 111

Which of the following is the method of choice for detecting alcohol dependence and hazardous drinking in primary care settings?


Exam Question Aug 2008

AUDIT is used in primary care settings as it accurately detects both alcohol dependence and hazardous drinking. CAGE is good at detecting dependence only.

Alcohol screening tools


A variety of tools have been devised to assist in the diagnosis of alcohol problems.

AUDIT (Alcohol Use Disorders Identification Test), was developed by the WHO as a simple method of screening for excessive drinking. The test consists of 10 questions and attempts to cover the three domains of harmful use, hazardous use, and dependence.

  • 10 item questionnaire
  • Takes about 2-3 minutes to complete
  • Has been shown to be superior to CAGE and biochemical markers for predicting alcohol problems
  • Minimum score = 0, maximum score = 40
  • A score of 8 or more in men, and 7 or more in women, indicates a strong likelihood of hazardous or harmful alcohol consumption
  • A score of 15 or more in men, and 13 or more in women, is likely to indicate alcohol dependence
  • AUDIT-C is an abbreviated form consisting of 3 questions

http://libdoc.who.int/hq/2001/WHOMSDMSB01.6a.pdf

FAST (Fast Alcohol Screening Test), is a short and rapid test with just 4 questions that was developed to be used in a busy medical setting.

  • 4 item questionnaire (see table below)
  • Minimum score = 0, maximum score = 16
  • The score for hazardous drinking is 3 or more
  • With relation to the first question 1 drink = 1/2 pint of beer or 1 glass of wine or 1 single spirits
  • If the answer to the first question is 'never' then the patient is not misusing alcohol
  • If the response to the first question is 'Weekly' or 'Daily or almost daily' then the patient is a hazardous, harmful or dependent drinker. Over 50% of people will be classified using just this one question

NumberQuestion
1MEN: How often do you have EIGHT or more drinks on one occasion?
WOMEN: How often do you have SIX or more drinks on one occasion?
2How often during the last year have you been unable to remember what happened the night before because you had been drinking?
3How often during the last year have you failed to do what was normally expected of you because of drinking?
4In the last year has a relative or friend, or a doctor or other health worker been concerned about your drinking or suggested you cut down?

http://alcoholism.about.com/od/tests/a/fast.htm

CAGE is a 4 question screening tool. Two or more positive answers suggests problem drinking.

The CAGE is a well known but recent research has questioned its value as a screening test two or more positive answers is generally considered a 'positive' result.

LetterQuestion
CHave you ever felt you should Cut down on your drinking?
AHave people Annoyed you by criticising your drinking?
GHave you ever felt bad or Guilty about your drinking?
EHave you ever had a drink in the morning to get rid of a hangover (Eye opener)?

SASQ (Single alcohol screening questionnaire), asks only one question, when was the last time you had more than x alcoholic drinks in one day? (Where x is 8 for men and 6 for women). An answer of within 3 months indicates harmful or hazardous drinking.

PAT (Paddington Alcohol Test), was developed for use in a busy A&E department to detect hazardous drinking. 

MAST (Michigan Alcoholism Screening Test) is useful for detecting dependent drinkers.

Rapid Alcohol Problem Screen 4 (RAPS4) Consists of four questions and has been found to be highly effective in detecting alcohol dependence. A 'yes' answer to at least one of the four questions suggests that your drinking is harmful.

LetterQuestion
R (remorse)Have you had a feeling of guilt or remorse after drinking?
A (amnesia)Has a friend or a family member ever told you about things you said or did while you were drinking that you could not remember?
P (performance)Have you failed to do what was normally expected of you because of drinking?
S (starter drinker behaviour)Do you sometimes take a drink when you first get up in the morning?

Psychopharmacology 110

Which of the following medications is affected by moisture and so cannot be included in a compliance aid?


Drug stability


The stability of drugs varies considerably (Church 2006). Some medications cannot be included in compliance aids as they can be affected by their environment. Some drugs tend to absorb moisture from the air which renders them ineffective. Light is known to accelerate this process.

Examples of drugs effected this way and so unsuitable for compliance aids include:-

  • Sodium valproate
  • Zopiclone
  • Venlafaxine
  • Topiramate
  • Methylphenidate
  • Mirtazapine
  • Olanzapine
  • Amisulpride
  • Aripiprazole

Church C (2006) How stable are medicines moved from original packs into compliance aids? The Pharmaceutical Journal Vol 276; 75-81.

Psychopharmacology 109

A 46-year-old man is seen by an occupation health doctor due to long-term sickness leave. He states chronic lower back pain prevents him from working but examination findings are inconsistent and the doctor suspects a non-organic cause of his symptoms. This is an example of a:



Somatoform and Dissociative disorders


Somatoform disorders

The somatoform disorders are a group of disorders characterised by physical symptoms that are presumed to have a psychiatric origin.

They are classified slightly differently by the ICD-10 and DSM-IV, see below

Categories of somatoform disorders in the ICD-10
Somatisation disorder
Undifferentiated somatoform disorder
Hypochondriacal disorder
Somatoform autonomic dysfunction
Persistent somatoform pain disorder
Other somatoform disorder
Somatoform disorder unspecified

Categories of somatoform disorders in the DSM-IV
Somatisation disorder
Conversion disorder
Hypochondriasis
Body dysmorphic disorder
Pain disorder
Undifferentiated somatoform disorder
Somatoform disorder not otherwise specified

Questions on these are common. Usually they test a candidate's ability to differentiate between the different types of somatoform disorder.

Somatisation disorder (Briquet's syndrome) is characterised by multiple physical complaints affecting many organ systems that cannot be explained by physical disorders. It is more common in women, and normally begins before the age of 30. It is inversely related to social class, and is therefore more common in those with low education and limited incomes.

Conversion disorder (referred to as dissociative disorders in the ICD-10) is characterised by a neurological complaint that is related to stress or conflict. It is more common in women and is uncommon in the elderly. It usually presents with weakness, paralysis, pseudoseizures, involuntary movements and sensory disturbances (e.g. Blindness). It is classically associated with the term La belle indifference which refers to the absence of distress despite the presence of a distressing symptom. 

Hypochondriasis is characterized by a patient's insistence that they suffer with a particular disease, despite evidence to the contrary.

Body dysmorphic disorder is characterized by the false belief or exaggerated perception that a part of the body is in some way defective. The most common area perceived to be affected is the skin, followed by the hair, nose, toes, and then weight.

Somatoform autonomic dysfunction includes:-

  • Da Costa's syndrome
  • Cardiac neurosis
  • Neurocirculatory asthenia
  • Dyspepsia
  • Pylorospasm
  • Irritable bowel syndrome
  • Psychogenic flatulence
  • Psychogenic cough
  • Hyperventilation
  • Psychogenic frequency
  • Dysuria

Do not confuse the above with factitious disorder. In factitious disorder a patient will intentionally (deliberately) feign symptoms. Munchausen syndrome is another name for factitious disorder.

Dissociative disorders

Dissociative disorders are characterised by the loss of integration between memories, identity, immediate sensations, and control of bodily movements.

Previously referred to as 'hysteria' (a term best avoided now), dissociative disorders usually occur suddenly in response to a trauma or other intolerable situation. They tend to remit spontaneously after a few weeks to months.

A diagnosis requires (ICD-10):

  • Loss of integration (partial or complete) between memories, identity, sensations and control of bodily movements
  • No evidence of a physical cause to explain the symptoms
  • Evidence for psychological causation (if none then the diagnosis should remain provisional)

Subtypes include:

  • Dissociative amnesia
  • Dissociative fugue
  • Dissociative stupor
  • Trance and possession disorders
  • Dissociative disorders of movement and sensation
  • Dissociative motor disorders
  • Dissociative convulsions (pseudoseizures)
  • Dissociative anaesthesia and sensory loss
  • Mixed dissociative disorders
  • Other dissociative disorders (includes Gansers syndrome and multiple personality disorder)