Positive Psychology

Webinar on Adverse Events in Psychopharmacology by Dr. Paul Putman

The highest hope for treatment with psychoactive medications is resolution or amelioration of targeted syndromes but adverse events still occur at incidences greater than desired. These should be anticipated and addressed prior to treatment and not just following their occurrence.

It is important to review the general assessment of and response to adverse events plus discontinuation syndrome, serotonin syndrome, tardive dyskinesia, extrapyramidal syndrome, rash, suicidality and neuroleptic malignant syndrome.

Two major adverse events to be tracked are anticipate the issue and address it prior to the treatment.

A few adverse events to monitor are as under:
Side Effect
Withdrawal syndrome
Discontinuation syndrome
Allergic reaction

The general assessment of adverse events comprises of comprehensive review at the initial stage, problem oriented review of systems and triage. It becomes important to determine compliance for missed doses, extra doses and inaccurate doses.

One needs to have a balance in life while being cautious of the adverse effects. Discontinuation syndrome was identified in early 1980s. Different types of discontinuation syndromes are SSRIs, SNRIs, MAOIs and TCAs.

Certain symptoms of discontinuation syndromes are:
Paresthesia – “electric shocks”

Effects of Discontinuation Syndrome:

May involve loss of clinical benefit and mood swing.
May occur from single missed dose.
Very scary for unwarned patients
Minimize risk by choosing longer half-lives.

Discontinuation Syndrome can be treated by restoring the missing medication.

DC Syndrome Alternative Strategy

Change from shorter half-life med to one with longer half-life
Must add longer half-life med to shorter one initially
Continue both until SSSL of new agent reached
Then, DC both meds simultaneously
Longer half-life agent will self taper
Be sure patient does not have bipolar disorder

Serotonin Syndrome (SS)
Serotonin Syndrome is caused with High CNS Serotonin or usage of one or more meds. It may cause agitation and delirium

Psychiatric Serotonergic Medications

Antidepressants – SSRIs, SNRIs
Second Generation Antipsychotics
Weight loss medications (Belviq [lorcaserin]) 

Migraine Treatments for Serotonergic include triptans and ergotamine.

Serotonin Syndrome Drug-Drug Interactions

CYP2D6 inhibition : fluvoxamine, fluoxetine, paroxetine, bupropion, sertraline, HIV antivirals (ritonavir), ziprasidone (weak)

CYP3A4 inhibition: fluvoxamine, norfluoxetine, verapamil, erythromycin.

Serotonin Syndrome Diagnostic Tools

Hunter Criteria: focus on physical symptoms.
Sternbach Criteria: more mental status changes.
Radomski Criteria: Sternbach revision with severity.

Serotonin Syndrome Differential Diagnosis

Neuroleptic Malignant Syndrome.
CNS Infection.
Anticholinergic Poisoning.

Treatment of Serotonin Syndrome is discontinuation of all Serotonergic Agents. SE Antiemetics must be avoided.

Neuroleptic Malignant Syndrome (NMS)

NMS is rare about – 0.02-0.03%. Its mortality rate is 5.6%.

Neuroleptic Malignant Syndrome Diagnosis includes:

Early altered mental status.
Must distinguish from catatonia.

Neuroleptic Malignant Syndrome Differential Diagnosis includes:

CNS infections and disease
Malignant hyperthermia from anesthetics
Abrupt DC of dopamine agonists
Heat stroke
Serotonin syndrome
Central anticholinergic syndrome
Lithium intoxication

Neuroleptic Malignant Syndrome Treatment includes:
Discontinue dopamine blocking agent(s)
Respiratory and volume support
Monitor electrolytes
Emergency hospital-based intensive treatment always needed.

Acute Dystonic Reaction (ADR)

ADR is acute, it causes sustained muscle contraction (cramp) and crisis of oculogy. It can be reversed with oral or IM anticholinergic medications like Diphenhydramine and Benztropine

Extrapyramidal Syndrome (EPS)

EPS is different from Parkinson’s disease. Dopamine transporter protocol is used to differentiate Parkinson’s disease from EPS. Treatment of EPS includes benztropine, trihexyphenidyl and amantadine. Side effects may include congnitive impairment, dry mouth, constipation and urinary retention.

Patients suffering from these diseases are highly prone to suicidal tendencies.

Suicidality: Research Reports

Rare increase in suicidality, along with treatment efficacy, associated with active antidepressant treatment in children and adolescents.
RCTs of seven antidepressants showed no difference in rates of suicide and attempted suicide between active drug, active comparators, and placebo.
Pharmacoepidemiologic studies have shown antidepressants to provide protective effects against suicidal events for patients of all ages.
Longitudinal data from treatment of major depression with fluoxetine and venlafaxine in adults, geriatric patients, and youths showed a significant reduction in suicidality, plus additional clinical benefit.
Data also showed that in youths, depressive symptoms sometimes improved without a reduction in pretreatment suicidality.
Meta-analyses of RCTs found support for fluoxetine use in children and adolescents.

Concerns about Suicidality

Benzodiazepines may worsen suicidality when used without antidepressants.
Comorbid substance abuse significantly increases suicide risk.
Nontreatment factors, including high affective lability, correlated with suicidality.
Early suicidality may go unrecognized as treatment proceeds and be misattributed as adverse event.

Measures to treat suicidality

Assess every patient at every contact for suicidality.
Explain FDA warnings to patients and families prior to prescription.
Emphasize individualized treatment plans to minimize the risk of self-harm.

Summarizing the take aways of the webinar:

Adverse Events occur at incidences greater than desired.
One should anticipate and discuss at every visit.
Document complete ROS during initial assessment so follow-up review during appointments can clarify emergence of adverse events.

Full history will clarify compliance and interference of new treatments from other providers.
OTC medications
prn medications

Discontinuation Syndrome may be iatrogenic or due to poor compliance, but can be effectively managed if anticipated.

SS is not idiopathic but specifically related to high serotonin levels from dose, polypharmacy or drug–drug interactions.

TD may develop from the use of all antipsychotic medications and usually permanent, despite new treatments that reduce symptoms.

Antipsychotics should never be prescribed for any indication, even briefly, without fully disclosing the risk of TD.

NMS is a rare, potentially lethal complication of dopamine antagonists that is difficult to distinguish from catatonia during psychosis; may also be confused with SS.

Despite warnings of increased suicidality for many medications, this risk has not always been confirmed.

Effectively manage risk by fully evaluating suicidality at every single patient contact so that individualized treatment plans can be developed and altered as necessary.

For those who missed the webinar can refer the same here –

The webinar was hosted on Groupthera powered by Psychonline. In case if you would also like to organize the online webinar, you may explore

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