The thing to remember with both alcohol and benzodiazepine withdrawal is that THEY CAN KILL YOU!
What to watch out for
Withdrawal seizures and alcoholic hallucinosis (hallucinations that develop within 12 – 24 h and resolve within 24 – 48 h)
Delirium Tremens (DTs): hallucinations, disorientation, tachycardia, hypertension, fever, agitation, and diaphoresis. Symptoms can persist for up to 7d
Wernicke’s Encephalopathy: Happens in hours to days, it has a classic triad
- Encephalopathy: profound disorientation, indifference and inattentiveness
- Oculomotor dysfunction: nystagmus, lateral rectus palsy, conjugate gaze palsies (affecting the CN III, VI and VIII nuclei)
- Gait ataxia: affecting the vermis of the cerebellum
How it works
Since alcohol and benzodiazepines both work on the GABA receptor (potentiating the effect of GABA by increasing the frequency of channel opening) they are cross-reactive. This means that you can treat alcohol withdrawal with a tapering dose of benzos (and you can treat benzo withdrawal also with a tapering dose of more benzos).
The thing to watch out for with someone who has chronically used benzodiazepines and has suddenly stopped is that the onset of symptoms will depend on the half-life of that particular drug.
- Alprazolam (Xanax): 10 – 20 h
- Lorazepam (Ativan): 10 – 25 h
- Clonazepam (Rivotril): 20 – 50 h
- Diazepam (Valium): 30 – 200 h
To minimize benzodiazepine withdrawal symptoms if someone has extended use (>3 months): taper by 1-20% over 6 or more weeks and/or switch to longer-acting agents.
There are 4 main dopamine pathways in the brain:
- Nigro-Striatal: substantial nigra to basal ganglia, involved in movement (what gets affected to cause EPS: tardive dyskinesia, akatisia)
- Meso-Limbic: VTA to nucleus accumbens, “reward” pathway (causes the positive symptoms of schizophrenia)
- Meso-Cortical: VTA to cortex, motivation and emotional response (thought to cause the negative symptoms of schizophrenia)
- Tubulo-Infundibular: hypothalamus to posterior pituitary (hypoprolactinemia in untreated individuals, but D2 blockade with antipsychotics can cause a hyperprolactenemia)
Antipsychotic medication can be divided into 2 classes
- Typical/First Generation
- Atypical/Second Generation
Typicals are characterized by strong D2 antagonism in the mess-limbic and meso-cortical pathways. This can also lead to significant extrapyramidal symptoms (EPS). They also have strong CYP-450 metabolism (which means lots of interactions with other drugs and grapefruits).
- High-potency typicals: only slightly anticholinergic & minimally sedating but have more weight gain and a higher risk of EPS
- Low-potency typicals: more quite sedating and more anticholinergic (bradycardia, GI upset) but have a lower risk of EPS
Atypicals have less risk for EPS, but carry a higher risk for metabolic side-effects and weight gain. While they bind to D2 receptors (like typicals), atypicals have higher affinity for serotonin (5HT) receptors.
Clozapine is a little different from the other atypicals in that is has been shown to have a shorter half-life, which is thought to be why it doesn’t produce as many EPS. However it has the very specific (and serious) risk of agranulocytosis.