Tips and pearls

Treatment for PMDD (in the absence of true MDD and other anxiety disorders) exists through FDA approvals for Sarafem (fluoxetine) and Zoloft (sertraline) in the US

PMEs of existing MDD can be clinically treated by facilitating luteal phase serotonin, perhaps by increasing SSRI or SNRI monotherapy doses during the luteal phase and then reducing it again

Two-minute tutorial

Tardive dyskinesia

Long-term blockade of D2 receptors in the nigrostriatal dopamine (DA) pathway can cause upregulation of those receptors, which may lead to the hyperkinetic motor condition known as TD

Often characterized by facial and tongue movements (e.g., tongue protrusions, facial grimaces, chewing) as well as quick, jerky limb movements

This upregulation may be the consequence of the futile attempt of the neuron to overcome drug-induced blockade of its D2 receptors. Notice the increase in receptors in the image to the right in the following figure:

Figure 2.1. Upregulation of receptors in TD.

Tardive dyskinesia facts

17%–28% untreated, drug-naïve schizophrenics or in their normal unaffected twins, may show idiopathic, non-drug-related dyskinesia

TD occurs more often with typical antipsychotics but is clearly possible with atypical antipsychotics

As an example, risperidone’s annual incidence for TD is 0.4% compared to that of 5% for typical antipsychotics

D2 receptor antagonism in the striatum is the principal etiology suspected in TD

Damage to striatal GABA interneurons, and cholinergic interneurons, is a likely cause of TD in some cases

Outside D2 receptor antagonism, the atypical antipsychotics affect other receptors (5-HT2A antagonism), which may mitigate and lessen TD risk. They are associated with less risk of causing structural damage and provoking persistent, dynamic alterations in neurotransmitter systems involved in motor control

Brain morphometric changes also differ, where typical antipsychotics may lead to increased caudate, putamen, and thalamus volumes, and atypical antipsychotics may only lead to increased thalamus volumes suggesting less risk of neurodegenerative brain changes in the basal ganglia with these agents

Tardive dyskinesia treatments

If the patient is on a typical antipsychotic, a switch to an atypical antipsychotic may be warranted

• – Discontinue anticholinergic therapy as this may lower TD movements

• – Switch to clozapine (Clozaril/Fazaclo/Versacloz) as it has the lowest TD risk in this class

Initiate a suppressive therapy with a conventional typical antipsychotic as increasing muscle rigidity (parkinsonism) may lower TD symptoms by “masking” TD movements

Experimentally use tetrabenazine, donepezil, melatonin, branched-chain amino acids, dextromethorphan, vitamin E, or vitamin B6

Risk relapse and consider staying on the antipsychotic but with a dose reduction

Some patients with localized TD may respond to botulinum toxin (Botox) injections

Figure 2.2. TD treatment algorithm.¹

Posttest self-assessment question and answer

Which of the following are approved treatments for PME of existing depressive disorders?

A. Fluoxetine

B. Sertraline

C. Desvenlafaxine

D. Bupropion

E. A and B

F. None of the above

Answer: F

Fluoxetine and sertraline are approved for PMDD, and there are no current approvals for the clinical scenario of PME of existing depressive disorder.

In conclusion, the diagnostic criteria for PMDD, per the DSM-V, include:

1. In the majority of menstrual cycles, at least five symptoms must be present in the final week before the onset of menses, start to improve within a few days after the onset of menses, and become minimal or absent in the week after menses

2. One or more of the following symptoms must be present:

Marked affective lability (e.g., mood swings, feeling suddenly sad or tearful, or increased sensitivity to rejection)

Marked irritability or anger, or increased interpersonal conflicts

Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts

Marked anxiety, tension, and/or feelings of being keyed up or on edge

3. One or more of the following symptoms must additionally be present, to reach a total of five symptoms when combined with the symptoms from #2:

Decreased interest in usual activities (e.g., work, school, friends, hobbies)

Subjective difficulty in concentration

Lethargy, easily fatigued, or marked lack of energy

Marked change in appetite, overeating, or specific food cravings

Hypersomnia or insomnia

A sense of being overwhelmed or out of control

Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of “bloating” or weight gain

These symptoms must have been met for most menstrual cycles that occurred in the preceding year

4. The symptoms are associated with clinically significant distress or inteference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home)

5. The disturbance is not merely an exacerbation of the symptoms of another disorder such as MDD, panic disorder (PD), persistent depressive disorder (dysthymia), or a personality disorder (although it may co-occur with any of these disorders)

References

1.Stahl SM. Antidepressants. In: Stahl’s Essential Psychopharmacology, 4th edn. New York, NY: Cambridge University Press, 2013; pp. 284–369.

2.Gupta S, Mosnik D, Black DW, Berry S, Masand PS. Tardive dyskinesia: review of treatments past, present, and future. Ann Clin Psych 1999; 11:257–66.

3.Margolese HC, Chouinard G, Kolivakis TT, et al. Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 1: Pathophysiology and mechanism of induction. Can J Psychiatry 2005; 9:541–7.

4.Margolese HC, Chouinard G, Kolivakis TT, et al. Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 2: Incidence and management strategies in patients with schizophrenia. Can J Psychiatry 2005; 50:703–14.

5.Stahl SM. Aripiprazole. In: Stahl’s Essential Psychopharmacology Prescriber’s Guide, 3rd edn. New York, NY: Cambridge University Press, 2009; pp. 45–50.

6.Steiner M, Pearlstein T, Cohen LS, et al. Expert guidelines for the treatment of severe PMS, PMDD, and comorbidities: the role of SSRIs. J Womens Health (Larchmt) 2006; 15:57–69.

7.American Psychiatric Association. American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 5th edn. Washington, DC: American Psychiatric Publishing, 2013.

8.Kornstein SG, Harvey AT, Rush AJ, et al. Self-reported premenstrual exacerbation of depressive symptoms in patients seeking treatment for major depression. Psychol Med 2005; 35:683–92.

9.Kim J, Donovan J, Schwartz T. Dextromethorphan for tardive dyskinesia. Intern Neuropsychiatr Dis J 2014; 2: 136–40.

¹ Margolese HC, Chouinard G, Kolivakis TT, et al. Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 2: Incidence and management strategies in patients with schizophrenia. Can J Psychiatry 2005; 50:703–14.

Patient file

The Case:

The other lady with a moving jaw

The Question:

How to determine the cause of movement disorder side effects?

The Psychopharmacological dilemma:

Finding an effective regimen for depression while managing movement disorder side effects