Approaches to Treatment- Biological Flashcards
Antipsychotics
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.
Limitations
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.
Atypical third generation drugs
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
Anxiolytics
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.
Anxiolytics- Limits
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.
Beta-blockers
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
Psychostimulants
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
Why not depressants?
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.
Psychostimulants: Limitations
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.
Summary
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.
Neurophysiological Techniques
Neurophysiological techniques can be used either to measure or modify brain activity
For measuring brain activity we use electroencephalography (EEG) or magnetoencephalography (MEG)
For modifying brain activity we can stimulate the brain using electric current or magnetic fields:
Electroconvulsive Therapy (ECT)
Deep Brain Stimulation (DBS)
Transcranial Direct Current Stimulation (tDCS)
Transcranial Magnetic Stimulation (TMS)
Electroconvulsive Therapy
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.
Electroconvulsive Therapy: Limits
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
Deep Brain Stimulation
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
Deep Brain Stimulation: Limits
Invasive
Haemorrhaging or excessive bleeding due to damage to blood vessels
Wound infection
Post-operative headache
Irritable mood
Not always successful
Expensive
Transcranial Direct Current Stimulation (tDCS)
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)
Transcranial Direct Current Stimulation: Limitations:
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
Transcranial Magnetic Stimulation (TMS)
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
Repetitive Transcranial Magnetic Stimulation (rTMS)
Limitations:
Headaches
Seizures
Discomfort during stimulation
No long-term adverse effects have been identified
Neurofeedback (aka “EEG Biofeedback”)
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
Neurofeedback (aka “EEG Biofeedback”): Advantages
Completely non-invasive
Relatively inexpensive
Evidence of successful treatment across a range of disorders, especially ADHD, epilepsy, MDD, GAD and Insomnia
Neurofeedback (aka “EEG Biofeedback”): Limits
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
Summary Neurophysiological Treatments
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.
Summary pt2
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)
Antidepressants
Monoamine oxidase inhibitors (MAOIs)
Inhibit activity of monoamine oxidase
Increases activity of neurons that utilise noradrenaline and serotonin.
Monoamine oxidase inhibitors (MAOIs): Limitations:
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
Tricyclics
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
Selective Serotonin Reuptake Inhibitors (SSRIs)
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.
Antidepressants Controversy
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).
Antidepressant Effectiveness
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.
Read et al. (2014)
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%)
Ketamine
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?
