Approaches to Treatment- Biological

Question 1

Antipsychotics

Answer 1

Phenothiazines

Originally developed to calm patients facing surgery

Early 1950’s allowed schizophrenic patients live outside hospital

Work by blocking dopamine receptors

Reduce feelings of aggression or anxiety within a few hours but take several days or weeks to reduce other symptoms.

Question 2

Limitations

Answer 2

Effective in treating positive symptoms
Hallucinations, excitement, thought disorder, delusions.

No effect on negative symptoms

Strong side effects may cause patients to discontinue with medication or relapse.

Extrapyramidal side effects (involuntary muscle contractions, parkinsonism), Anticholinergic side effects (blurred vision, low blood pressure, constipation), and neuroleptic malignant syndrome.

Atypical 2nd generation antipsychotics such as Clozapine have little liability to induce extrapyramidal side effects though it can lead to a dangerously low white blood cell counts.

Question 3

Atypical third generation drugs

Answer 3

Partial agonists
Drugs which have high affinity for a receptor (in this case dopamine receptors) but activate it less than the related neurotransmitter.

One possible mechanism of action is to raise dopaminergic activity in the pre-frontal cortex and lower activity in key areas of the limbic system such as the nucleus accumbens

Therefore more effective in treating both positive and negative symptoms of schizophrenia

Question 4

Anxiolytics

Answer 4

Benzodiazepines

Used to reduce severe anxiety.

Act by facilitating the activity of GABA

Inhibitory neurotransmitter related to fear and anxiety.

Anxiolytic, sedative and hypnotic effects
Also muscle-relaxant and anticonvulsant properties.

Question 5

Anxiolytics- Limits

Answer 5

Can only be prescribed for short periods
Highly addictive - Can result in tolerance and dependence

Withdrawal effects include
Apprehension and anxiety
Tremor
Muscle twitching

Only offer symptom relief
Does not affect underlying psychological or emotional causes.

Question 6

Beta-blockers

Answer 6

Most commonly used in the treatment of high blood pressure

Blocks the effect of stress hormones adrenaline and noradrenaline

Similar efficacy as benzodiazepines on anxiety and panic attack frequency though evidence for other, social anxiety measures, inconclusive.

Side effects less severe than benzodiazepines and not believed to be addictive.

Only offer symptom relief
Does not affect underlying psychological or emotional causes

Question 7

Psychostimulants

Answer 7

Methylphenidate (Ritalin)
Used in the treatment of ADHD

Act as dopamine and/or noradrenalin reuptake inhibitors.

Both dopamine and noradrenalin are important in regulation of attention and executive function

Short acting and administered 2 to 3 times daily.

Effective in providing short-term sustained attention, lowered activity level, and reduced impulsivity

Question 8

Why not depressants?

Answer 8

Depress the central nervous system thus reducing alertness and control.

This has a negative effect on executive function.

Psychostimulants stimulate parts of the brain that allow inhibition of hyperactive and impulsive behaviour.

Unlike depressants, they don’t reduce functioning of other parts of the brain.

Question 9

Psychostimulants: Limitations

Answer 9

Increase in BP and heart rate
Loss of appetite
Disturbed sleep patterns
Irritability

Impaired Socialisation (the “zombie effect)
Social withdrawal
Diminished social interaction/social play
Over focused behaviour
Often overlooked/mistaken for reduction in ADHD symptoms.

Question 10

Summary

Answer 10

Psychotropic Drugs have been used to treat a number of disorders.

These include Depression, Schizophrenia, Anxiety, and ADHD

The exact mechanism of action for each drug is not always known and a number of patients can prove resistant to their effects.

They are also often associated with a number of negative side effects which can be both physical and mental.

Question 11

Neurophysiological Techniques

Answer 11

Neurophysiological techniques can be used either to measure or modify brain activity

For measuring brain activity we use electroencephalography (EEG) or magnetoencephalography (MEG)

Question 12

For modifying brain activity we can stimulate the brain using electric current or magnetic fields:

Answer 12

Electroconvulsive Therapy (ECT)
Deep Brain Stimulation (DBS)
Transcranial Direct Current Stimulation (tDCS)
Transcranial Magnetic Stimulation (TMS)

Question 13

Electroconvulsive Therapy

Answer 13

Patient anesthetized

Electrodes placed on scalp, most often on the non-dominant hemisphere side, followed by a 70 – 150 volt shock which triggers a seizure.

Involves three treatments a week until maximum improvement is seen (usually between 6 and 12 treatments in total)

Possible action via an increase in GABA and neuropeptide Y related to raised seizure threshold.

Question 14

Electroconvulsive Therapy: Limits

Answer 14

Short term:
Risks associated with being given an anaesthetic
Epileptic fit

Long term:
Brain damage
Retrograde amnesia
Though short term use believed to be safe.

Effectiveness:
High relapse rate.
Effects would seem to limited to no more than 4 weeks.
More effective when used in combination with antidepressants

Question 15

Deep Brain Stimulation

Answer 15

Implants a ‘brain pacemaker’

This pacemaker sends an electrical signal to parts of the brain that need to be stimulated

Internal pulse generator – implanted under skin – sends out electrical pulse

Pulse travels up the extension to the lead

Lead is insulated wire with electrodes implanted in the to-be-stimulated brain region

Question 16

Deep Brain Stimulation: Limits

Answer 16

Invasive

Haemorrhaging or excessive bleeding due to damage to blood vessels

Wound infection

Post-operative headache

Irritable mood

Not always successful

Expensive

Question 17

Transcranial Direct Current Stimulation (tDCS)

Answer 17

Delivers direct current to a brain region through electrodes placed on the scalp

Battery powered device delivers constant current

Electrode in a region of interest

Reference electrode to complete the circuit

Can be used to increase neuronal excitability (anodal stimulation)

Or decrease neuronal excitability (cathodal stimulation)

Question 18

Transcranial Direct Current Stimulation: Limitations:

Answer 18

Low spatial resolution – large portions of brain will be activated or suppressed

Skin irritation

Cognitive impairments/improvements appear transient

No long-term adverse effects have been identified

Question 19

Transcranial Magnetic Stimulation (TMS)

Answer 19

Applies rapidly changing electromagnetic fields to induce electrical currents

When applied repetitively (rTMS) it can increase or decrease cortical excitability

Low frequency stimulation inhibits

High frequency stimulation activates

Question 20

Repetitive Transcranial Magnetic Stimulation (rTMS)

Limitations:

Answer 20

Headaches
Seizures
Discomfort during stimulation
No long-term adverse effects have been identified

Question 21

Neurofeedback (aka “EEG Biofeedback”)

Answer 21

Participants/Patients modify their own brainwaves

Connected to EEG, with just a few electrodes

Shown a measure of their brain activity in real time

Learn how to voluntarily increase or decrease the amplitude or frequency of their brainwaves

Most protocols aim to increase alpha rhythm (10 Hz activity)

This rhythm is found to increase during meditation, e.g. during mindfulness meditation

Question 22

Neurofeedback (aka “EEG Biofeedback”): Advantages

Answer 22

Completely non-invasive
Relatively inexpensive

Evidence of successful treatment across a range of disorders, especially ADHD, epilepsy, MDD, GAD and Insomnia

Question 23

Neurofeedback (aka “EEG Biofeedback”): Limits

Answer 23

Significant proportion of individuals don’t show any benefit

Significant proportion of individuals don’t achieve the required level of control over their brainwaves

Experiments/trials have not been well controlled

Question 24

Summary Neurophysiological Treatments

Answer 24

ECT was originally developed for the treatment of schizophrenia, however is has proved to be more effective in treating depression.

DBS has been successfully used for many psychological disorders – most successfully for depression

tDCS has also been beneficial for depression – especially when combined with cognitive therapy

rTMS has had promising results for both Depression and Schizophrenia

Neurofeedback involves voluntary brain ‘training’ and has had success in treating many disorders including ADHD.

Question 25

Summary pt2

Answer 25

Our brains communicate both electrically and chemically

Psychoactive drugs alter the chemical messages; neurophysiological treatments alter the electrical messages

Neurophysiological techniques can directly alter brain activity both invasively (deep brain stimulation) or non-invasively (tDCS and TMS)

Neurophysiological techniques can also indirectly alter brain activity (neurofeedback)

Question 26

Antidepressants

Monoamine oxidase inhibitors (MAOIs)

Answer 26

Inhibit activity of monoamine oxidase

Increases activity of neurons that utilise noradrenaline and serotonin.

Question 27

Monoamine oxidase inhibitors (MAOIs): Limitations:

Answer 27

Generally less effective than more recent drugs for severe depression

Side effects
Cerebral Haemorrhage
Dangerous interactions with other drugs/foods

Can be effective where patient is not responding to other antidepressants

Question 28

Tricyclics

Answer 28

Named after their chemical structure which includes 3 carbon rings

Believed to act by blocking reuptake of dopamine, noradrenaline, and serotonin, though the action of some drugs in this class remains unknown.

Effective in the treatment of mild and severe depression.

Limitations
Number of side-effects including toxic effects on cardiovascular system

Question 29

Selective Serotonin Reuptake Inhibitors (SSRIs)

Answer 29

Selectively inhibit the re-uptake of serotonin.

As effective as tricyclics in treating mild depression

Fewer side effects

Safer for patients with glaucoma and in overdose.

Now also used in treatment of Anxiety and OCD.

Question 30

Antidepressants Controversy

Answer 30

Use of SSRIs such as Prozac have been linked to acts of violence and suicide.

Seroxat along with all other SSRIs with the exception of Prozac are now banned for prescription to under 18s in UK.

Reanalysis by Noury et al. (2015) found that harmful effects of Seroxat had been underreported in original study on adolescents by Keller et al. (2001).

Question 31

Antidepressant Effectiveness

Answer 31

Effectiveness of antidepressants modest

High relapse rate of 60% when medication ceases

Benefits wane whilst still taking drug

Gender effect – SSRIs tend to work better with women rather than men.

Question 32

Read et al. (2014)

Answer 32

Online survey in New Zealand of 1829 adults prescribed antidepressants.

Eight (out of 20) adverse effects were reported by over half the participants including:
Sexual difficulties (62%)
Feeling emotionally numb (60%)
Feeling not like themselves (52%)
Suicidality (39%)

Question 33

Ketamine

Answer 33

Alternative to serotonin related treatments.

Acts on glutamate
Key role in leaning, motivation and plasticity
May restore connections between damaged synapses caused by long term depression

Immediate effect. Intravenous administration of Ketamine hydrochloride lifted depressive symptoms within 2 hours (Zarate et al., 2006)

Esketamine recently licenced for use in UK as a nasal spray.

Limitations:
Possible danger of addiction

Possible psychotic side effects

Cystitis

Increases in blood pressure.

Is it just drug euphoria?