Sesión 3: My Friend The Whale 58

Of course, there is no such thing as emergency psychopharmacology for suicide prevention—at least not yet. Research opportunities and related hypotheses are available to advance this new clinical endeavor. The clinical need for emergency psychopharmacology for suicide prevention has never been greater. Since, as described on prior pages, suicide risk is highest in the immedi-

Continuity of Care for Suicide Prevention and Research

ate period after discharge from an emergency department or an inpatient psychiatry unit, this time interval is one window of opportunity to use psychopharmacology to aid in the prevention of suicide. Hereafter, these ideas will be fleshed out and related research suggested.

The known psychopharmacology of suicide is limited to two medications—clozapine and lithi- um. By statistically combining the results of several related clinical studies (i.e., meta-analysis), there is considerable support favoring the long-term use of lithium as an anti-suicide pharma- ceutical. 37, 38, 61, 297-303 _{The use of lithium to prevent suicide has not been tested by prospective,} randomized-control research. Moreover, lithium may produce deleterious and lasting effects on organ systems, mostly when lithium is taken for several years, and lithium is potentially lethal in overdose situations. 304, 305

The antipsychotic, clozapine, has been shown in a single large, multi-site, randomized controlled trial (RCT) to reduce recurrent suicide behaviors generally and only in patients with schizophre- nia. 306, 307 _{This trial compared clozapine to an alternative antipsychotic, olanzapine. The anti-sui-} cide properties of these two antipsychotics have not been compared to the anti-suicide properties of placebo. What is more, it is possible that olanzapine is worse as much as clozapine is better. Another possibility is that clozapine success was more due to its exacting administration than to any intrinsic pharmacological properties.

Although the RCT attempted to control for differences in administration, clozapine, in comparison to olanzapine, requires a very slow up taper dosing schedule of administration and considerable clinical vigilance to detect agranulocytosis, a potentially life-threatening blood disorder. Because of significant risk of agranulocytosis, clozapine is most often used as the antipsychotic of last resort, and the possible appearance of clozapine’s adverse effects requires close clinical monitoring. 308, 309 Thus, the added, necessary psychosocial relationship with clinicians administering clozapine may be contributing to the overall outcome in this RCT. Clearly, clozapine’s effectiveness in reducing suicide behaviors and suicide deaths specifically requires support from additional research. Evi- dence favoring other pharmaceuticals is nearly absent.

Persuasive evidence that antidepressants have anti-suicide properties has yet to be found. There have been no randomized controlled trials to test the hypothesis that antidepressants are effective in reduc- ing suicide attempts, suicide acts, or suicide deaths. Mann and others did a comprehensive review of suicide prevention strategies and concluded that physician education in depression recognition and treatment reduces suicide rates in adult patients if they adhere to long-term treatment. 214 _However, during the start-up phase of administration, suicide ideation, particularly in children and adolescents, may increase. 50, 154, 310-314 _{Antidepressants have not been associated with suicide deaths.} 50, 154, 310-314 The efficacy of antidepressants may be assessed by their discontinuation. For adults, there is strong evidence that stopping antidepressants increases suicide risk. 38, 39, 310, 315-317 _{Likewise, antide-} pressant non-adherence is associated with suicide attempts. 37, 38, 214, 315, 316, 318-320

Busch and Fawcett make an important point based on case studies of patients that have died by suicide while hospitalized. Similar outpatient investigations led them to the same conclusion.

Fawcett finds that there is a profile of patient attributes that characterizes inpatients that are at high risk for suicide. High “psychic anxiety,” profound sleep disturbance, rapidly fluctuating clinical course, and inability to experience pleasure are all on the list. 146, 148, 151, 280, 281 _{Busch and Fawcett} may well have identified a subset of patients that are at high risk for suicide for which there may be an indication for using emergency psychopharmacology to prevent suicide attempts and sui- cide. These hypotheses are important because medications are rapidly effective for anxiety and sleep as well as the agitation associated with a fluctuating clinical course. 176 _{These hypotheses} have not been tested. If they prove to be true, the results have many implications for the way po- tentially suicidal inpatients and outpatients are treated and managed.

Before describing a path forward, one more piece of background information needs to be restated. Without question, suicide attempts and suicide acts are life and death situations potentially. This realization is critical to accepting the proposal for using emergency psychopharmacology for sui- cide prevention because any pharmaceutical used may have most serious adverse effects including death by intentional overdose or from infrequent or rare physiologic actions inherent to a particu- lar pharmaceutical. Accordingly, the use of pharmaceuticals for suicide prevention must weigh the consequences of doing nothing pharmacologically and relying solely on all other means for sui- cide prevention. Surely, suicide prevention requires as many effective tools as can be mobilized. Where to start? Inpatient units are among the safest places to begin research of the sort to be sug- gested. The various hypotheses suggested by Busch and Fawcett mentioned above can be evalu- ated by randomized methods. For many, suicide risk is associated with a discrete time interval during which psychopharmacology may augment other anti-suicide interventions. One obvious experiment is similar to the trial comparing clozapine to olanzapine. In the proposed similarly de- signed trial, patient participants could be randomized to one group that receives short-term lithium plus treatment as usual or to the control condition that receives only treatment as usual. Suicide behaviors could be assessed as 3, 6, and 12 months. This sort of model, randomized controlled trial can be applied with other pharmaceuticals thought to have significant anti-suicide properties. Lithium is used as an example.

Section-at-a-Glance:

The mood stabilizer, lithium, the antipsychotic, clozapine, and any one of several rapidly acting, anti-anxiety agents (e.g., clonazepam, a benzodiazepine) are candidate pharmaceu- ticals for use in emergency psychopharmacology for suicide prevention. The use of any pharmaceutical for this purpose must consider the risk of death from suicide versus the risk of serious adverse effects from psychopharmacology versus the utility of various psy- chosocial interventions versus doing nothing. Suicide prevention requires as many tools as can be mobilized, particularly during the intervals of greatest suicide risk—after discharge from an emergency department or psychiatric inpatient unit. To determine if, during this critical period, psychopharmacology is a suicide prevention tool that augments the ef- fectiveness of other tools, new research is required. Suggested hypotheses and research designs are mentioned in the text above.

Continuity of Care for Suicide Prevention and Research

Section-related Recommendations:

• Use randomized methods to compare two groups of patient-subjects that differ- entially receive either the psychopharmacologic agent with possible anti-suicide properties plus treatment as usual or receive only treatment as usual. Investiga- tions of this sort best apply to a relatively short period of heightened suicide risk and increased suicide reattempt rates. Required sample sizes necessitate multi-site trials.

• Investigate therapeutic efficacy with studies of the outcomes of therapy discon- tinuation and non-adherence.

Inpatient Discharge Planning and the Transition